Couto-Pereira et al. Neonatal Interventions Affect Memory Reconsolidation no differences in the r... more Couto-Pereira et al. Neonatal Interventions Affect Memory Reconsolidation no differences in the reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of reconsolidation. Our results support a hippocampal-dependent mechanism for reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD.
El presente proyecto estudia la posible participacion de procesos neurales de sensibilizacion de ... more El presente proyecto estudia la posible participacion de procesos neurales de sensibilizacion de diferentes sistemas neurotransmisores centrales en la expresion de conductas analogas de sintomas de la ansiedad y la depresion. En el caso de la ansiedad y la generacion de conflictos, se pretende demostrar que el sistema gabaergico ejerce un rol critico en la generacion de un proceso de sensibilizacion para la expresion de comportamiento de miedo y de ansiedad. Bajo esta linea de razonamiento, tambien se evalua el desarrollo de un potencial proceso de sensibilizacion en las manifestaciones comportamentales analogas a sintomas depresivos e inducidas por la aplicacion de estresores inescapables. A tal efecto se determinara la posible participacion de un mecanismo opiaceo endogeno en el desarrollo de dicho proceso de sensibilizacion. Objetivo general: Estudiar la participacion de un proceso de sensibilizacion de determinados mecanismos neurales, inducida por distintos esquemas de estresor...
Pregnant rats from day 14 of pregnancy or pups were fed a control diet (24% casein) or a deprived... more Pregnant rats from day 14 of pregnancy or pups were fed a control diet (24% casein) or a deprived diet (8% casein) in order to obtain the following groups: 1) Control (C-C group); 2) Prenatal deprived (D-C group); 3) Postnatal deprived (C-D group); 4) Pre and postnatal deprived (D-D group). From 50 days of age on, all groups were fed a balanced commercial stock diet until 140 days of age. A significant reduction in corporal and brain weights was observed in C-D and D-D groups during deprivation and after nutritional recovery. Twenty-four day old deprived rats showed a decrease in brain noradrenaline (NA) content but no significant change in NA concentration. By the end of the deprivation period (50 days), brain NA levels tended to be reduced or increased in postnatal deprived rats, depending upon the method of expressing the results (microgram NA/whole brain or microgram NA/g fresh tissue, respectively). At 140 days of age, i.e., after 90 days of nutritional recovery, no differences were detected between deprived and control rats. However, conversion rate of [14C]tyrosine to brain catecholamines and tyrosine-hydoxylase activity were higher in D-D rats as compared with controls at this age. These results suggest that perinatal undernutrition produces, even after a prolonged period of nutritional recovery, a permanent activation of the central catecholaminergic system in adulthood. This fact may explain the different behavioral alterations described as a consequence of protein deprivation in early life.
It is well known that stress can affect mnemonic processes. In particular, stress before contextu... more It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdalar GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration...
Rats pretreated with gangliosides showed a significant enhancement of the anti-immobility effect ... more Rats pretreated with gangliosides showed a significant enhancement of the anti-immobility effect of desipramine (DMI) in the forced swimming test. Accordingly, an associated treatment of gangliosides and DMI for 7 days significantly enhanced beta-adrenergic down-regulation in the frontal cortex as compared with the effect of DMI alone. Gangliosides exerted an accelerating effect on the decrease of beta-adrenoceptor density induced by DMI, since the down-regulation phenomenon appeared after 3 days of treatment. Gangliosides did not affect the pharmacokinetics of DMI, since associated acute or prolonged treatments did not modify the brain levels of DMI as compared to the levels of animals that had received DMI alone. These results evidence a stimulating effect of gangliosides on the development of adaptative receptor changes induced by chronic DMI treatment.
, with details of the nature of the infringement. We will investigate the claim and if justified,... more , with details of the nature of the infringement. We will investigate the claim and if justified, we will take the appropriate steps.
Psychiatry and Neuroscience Update - Vol. II, 2017
Stress is a major risk factor in the etiology of several psychiatric diseases, such as anxiety di... more Stress is a major risk factor in the etiology of several psychiatric diseases, such as anxiety disorders and depression. On the other hand, a growing body of evidence has demonstrated that astrocytes play a pivotal role in the normal functioning of the nervous system. Hence, understanding the effects of stress on astrocytes is crucial for a better comprehension of stress-related mental disorders. Here, we describe the evidence showing astrocyte changes induced by stress in animals and how this plasticity could operate to induce behavioral sequelae. In addition, human data linking astrocytes with psychiatric disorders related to stress are also discussed. Altogether, the data indicate that both chronic and acute stressors are capable of changing the morphology and function of astrocytes in the brain areas that are known to play a critical role in emotional processing, such as the prefrontal cortex, hippocampus, and amygdala. Furthermore, different lines of evidence suggest that astrocyte plasticity may contribute to the behavioral consequences of stress.
The destabilization/reconsolidation process can be triggered by memory recall, allowing consolida... more The destabilization/reconsolidation process can be triggered by memory recall, allowing consolidated memories to be modified. We have previously reported that stress prior to fear conditioning induces memories that exhibit resistance to the engagement of some molecular events associated with the destabilization/reconsolidation process. Here, we evaluated whether stress could affect the expression of Lys-48 polyubiquitinated proteins within the basolateral amygdala complex, a phenomenon crucially linked to memory destabilization. As expected, a post-recall increase of Lys-48 polyubiquitinated proteins in control animals was observed; however, this phenomenon was prevented by stress exposure before fear conditioning. On the other hand, pre-recall administration of D-cycloserine -a positive modulator of NMDA sites capable of reverting memory resistance to pharmacological interference-, facilitated the increase of Lys-48 polyubiquitinated proteins in stressed animals. In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to furthercharacterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling,protein degradation and memory destabilization in stress-induced resistant memories.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fear extinction is defined as a decline in fear-conditioned responses following non-reinforced ex... more Fear extinction is defined as a decline in fear-conditioned responses following non-reinforced exposure to a fear conditioned stimulus, therefore the conditioned stimulus gains new predictive properties. Patients with anxiety related disorders (e.g.: PTSD) subjected to extinction-like exposure treatments often experience a relapse of symptoms. Stress is a risk factor for those psychiatric disorders and a critical modulator of fear learning that turns the memory resistant to the extinction process. Dendritic spines are the anatomical sites where neuronal activity reshapes brain networks during learning and memory processes. Thus, we planned to characterize the dynamics of synaptic remodeling before and after contextual fear extinction in the dorsal hippocampus (DH), and how this process is affected by a previous stress experience. Animals with or without previous stress were contextually fear conditioned and one day later trained in an extinction paradigm. Rats were sacrificed one da...
Methods and findings in experimental and clinical pharmacology, 1992
The inclusion of clonidine (CLO) induced a dose-dependent reduction of K(+)-evoked [3H] dopamine ... more The inclusion of clonidine (CLO) induced a dose-dependent reduction of K(+)-evoked [3H] dopamine ([3H]DA) release in slices from rat nucleus accumbens. This inhibition was clearly attenuated in animals previously administered desipramine daily (DMI, 10 mg/kg i.p.) during 21 days, but not in rats submitted to a persistent treatment with DMI during 10 days. However, the coadministration of adrenocorticotrophic hormone (ACTH, 50 IU/kg s.c.) and DMI (10 mg/kg i.p.) for 10 days provoked a clear decrease in the inhibition produced by alpha 2-adrenoceptor stimulation, while ACTH alone had no effect. These results may indicate that ACTH accelerates the onset of DMI-induced adaptive changes on central alpha 2-adrenoceptor in the mesolimbic area.
The idea that memories are not invariable after the consolidation process has led to new perspect... more The idea that memories are not invariable after the consolidation process has led to new perspectives about several mnemonic processes. In this framework, we review our studies on the modulation of memory expression during reconsolidation. We propose that during both memory consolidation and reconsolidation, neuromodulators can determine the probability of the memory trace to guide behavior, i.e. they can either increase or decrease its behavioral expressibility without affecting the potential of persistent memories to be activated and become labile. Our hypothesis is based on the findings that positive modulation of memory expression during reconsolidation occurs even if memories are behaviorally unexpressed. This review discusses the original approach taken in the studies of the crab Neohelice (Chasmagnathus) granulata, which was then successfully applied to test the hypothesis in rodent fear memory. Data presented offers a new way of thinking about both weak trainings and experimental amnesia: memory retrieval can be dissociated from memory expression. Furthermore, the strategy presented here allowed us to show in human declarative memory that the periods in which long-term memory can be activated and become labile during reconsolidation exceeds the periods in which that memory is expressed, providing direct evidence that conscious access to memory is not needed for reconsolidation. Specific controls based on the constraints of reminders to trigger reconsolidation allow us to distinguish between obliterated and unexpressed but activated long-term memories after amnesic treatments, weak trainings and forgetting. In the hypothesis discussed, memory expressibility--the outcome of experience-dependent changes in the potential to behave--is considered as a flexible and modulable attribute of long-term memories. Expression seems to be just one of the possible fates of re-activated memories.
The modulatory effect of conditioned opiate analgesia on immobility during a forced swim situatio... more The modulatory effect of conditioned opiate analgesia on immobility during a forced swim situation was studied. Animals submitted to inescapable shock (IS) were exposed 6 days later to a similar or different shock application context and, immediately after, tested in either hot plate test or forced swim test. A conditioned analgesia was observed only on animals submitted to the shock context. This conditioned analgesia was blocked by naloxone administration injected either before IS or before context exposure. In the same way, animals exposed to shock context and immediately forced to swim showed an increase in the immobility time, which was sensitive to naloxone injection before IS as well as before context exposure. These results and additional data referring to naloxone effect on inactivity during IS are discussed in terms of the possible role of endogenous opiate in analogous behavior expressed during different aversive experiences.
Escape performance in a shuttie-box task was evaluated in rats chronically exposed to a series of... more Escape performance in a shuttie-box task was evaluated in rats chronically exposed to a series of unpredictable stressors either during 14 or 7 consecutive days. Failure in escape responses was observed when animals were subjected to both regimes of variable aversive situations. The association between chronic exposure to unpredictable stressors with imipramine resulted in a significant reversal of escape deficits. Furthermore, animals submitted to repeated immobilization sessions during 7 days presented similar escape response to control rats. A possible involvement of beta-adrenergic sites on this behavioral response is discussed. Shuttle-box Escape deficit Chronic variable stress Imipramine
Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. Th... more Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. This occurs as a result of profound functional and morphological changes of different neuronal circuits, including modifications in the plasticity and architecture of hippocampal synapses. Such alterations can be implicated in the genesis and progression of dementia associated with neurodegenerative diseases including Parkinson-like symptoms. There are few studies regarding cognitive changes in nigrostriatal animal models. The aim of this study was to characterize the onset of memory deficit after induction of neurotoxicity with 6-hydroxydopamine (6-OHDA) and its correlation with hippocampal dysfunction. For this, we bilaterally microinjected 6-OHDA in dorsolateral Caudate-Putamen unit (CPu) and then, animals were tested weekly for working memory, spatial short-term memory, and motor performance. We evaluated tyrosine hydroxylase (TH) as a dopamine marker, aldehyde dehydrogenase 2 (ALDH2),...
It is known that a consolidated memory can return to a labile state and become transiently mallea... more It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiologica...
The present research was conducted to evaluate the influence of different stress schedules on beh... more The present research was conducted to evaluate the influence of different stress schedules on behaviors displayed during both phases of the forced swim test (FST). In addition, the involvement of an opiate mechanism in the behavioral consequences of chronic restraint was investigated. Exposure to a single, but not to chronic, restraint event induced an increase in the immobility score obtained during the 10-min initial swimming exposure (initial test) of the FST. Animals submitted to a previous regime of repeated restraint showed a significant increase in immobility during the 5-min second swimming exposure (retest period) of this behavioral task. However, naloxone (NAL) administered before each of the seven restraint events, blocked the higher immobility observed in chronically stressed rats during the retest period suggesting the involvement of an opiate mechanism. Results concerning the effect of chronic stress on the behavior displayed during the FST were discussed with reference to previous reports which have proposed that immobility performed during the retest period of the FST represents an efficient adaptive response in this inescapable aversive experience.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.
In agreement with previous reports, low doses of apomorphine (10-50 micrograms/kg, 5 min before t... more In agreement with previous reports, low doses of apomorphine (10-50 micrograms/kg, 5 min before test) produced a dose-dependent decrease in motor activity of control rats. This effect was markedly attenuated 24 h after a prolonged immobilization stress (2 h daily during 7 days). A single stress session had no effect on motor activity. These behavioral observations suggest a reduced sensitivity of presynaptic dopamine receptors after chronic stress.
Couto-Pereira et al. Neonatal Interventions Affect Memory Reconsolidation no differences in the r... more Couto-Pereira et al. Neonatal Interventions Affect Memory Reconsolidation no differences in the reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of reconsolidation. Our results support a hippocampal-dependent mechanism for reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD.
El presente proyecto estudia la posible participacion de procesos neurales de sensibilizacion de ... more El presente proyecto estudia la posible participacion de procesos neurales de sensibilizacion de diferentes sistemas neurotransmisores centrales en la expresion de conductas analogas de sintomas de la ansiedad y la depresion. En el caso de la ansiedad y la generacion de conflictos, se pretende demostrar que el sistema gabaergico ejerce un rol critico en la generacion de un proceso de sensibilizacion para la expresion de comportamiento de miedo y de ansiedad. Bajo esta linea de razonamiento, tambien se evalua el desarrollo de un potencial proceso de sensibilizacion en las manifestaciones comportamentales analogas a sintomas depresivos e inducidas por la aplicacion de estresores inescapables. A tal efecto se determinara la posible participacion de un mecanismo opiaceo endogeno en el desarrollo de dicho proceso de sensibilizacion. Objetivo general: Estudiar la participacion de un proceso de sensibilizacion de determinados mecanismos neurales, inducida por distintos esquemas de estresor...
Pregnant rats from day 14 of pregnancy or pups were fed a control diet (24% casein) or a deprived... more Pregnant rats from day 14 of pregnancy or pups were fed a control diet (24% casein) or a deprived diet (8% casein) in order to obtain the following groups: 1) Control (C-C group); 2) Prenatal deprived (D-C group); 3) Postnatal deprived (C-D group); 4) Pre and postnatal deprived (D-D group). From 50 days of age on, all groups were fed a balanced commercial stock diet until 140 days of age. A significant reduction in corporal and brain weights was observed in C-D and D-D groups during deprivation and after nutritional recovery. Twenty-four day old deprived rats showed a decrease in brain noradrenaline (NA) content but no significant change in NA concentration. By the end of the deprivation period (50 days), brain NA levels tended to be reduced or increased in postnatal deprived rats, depending upon the method of expressing the results (microgram NA/whole brain or microgram NA/g fresh tissue, respectively). At 140 days of age, i.e., after 90 days of nutritional recovery, no differences were detected between deprived and control rats. However, conversion rate of [14C]tyrosine to brain catecholamines and tyrosine-hydoxylase activity were higher in D-D rats as compared with controls at this age. These results suggest that perinatal undernutrition produces, even after a prolonged period of nutritional recovery, a permanent activation of the central catecholaminergic system in adulthood. This fact may explain the different behavioral alterations described as a consequence of protein deprivation in early life.
It is well known that stress can affect mnemonic processes. In particular, stress before contextu... more It is well known that stress can affect mnemonic processes. In particular, stress before contextual fear conditioning induces a memory which exhibits resistance to being interfered with by Midazolam (MDZ) when applied after memory retrieval. Moreover, stress exposure strongly affects GABAergic transmission within the Basolateral Amygdala Complex (BLA), a brain structure critically involved in fear memory processing. The present study evaluated the involvement of GABAergic signaling within the BLA on the induction of resistance to memory reconsolidation interference. Results showed that MDZ administered intra-BLA before stress prevented the induction of resistance to the interfering effect of systemic administration of both MDZ and Propranolol on fear memory reconsolidation, when both applied after memory retrieval. The blockade of amygdalar GABA-A receptors by the antagonist Bicuculline (BIC) before memory encoding induced resistance to interference by post-recall MDZ administration...
Rats pretreated with gangliosides showed a significant enhancement of the anti-immobility effect ... more Rats pretreated with gangliosides showed a significant enhancement of the anti-immobility effect of desipramine (DMI) in the forced swimming test. Accordingly, an associated treatment of gangliosides and DMI for 7 days significantly enhanced beta-adrenergic down-regulation in the frontal cortex as compared with the effect of DMI alone. Gangliosides exerted an accelerating effect on the decrease of beta-adrenoceptor density induced by DMI, since the down-regulation phenomenon appeared after 3 days of treatment. Gangliosides did not affect the pharmacokinetics of DMI, since associated acute or prolonged treatments did not modify the brain levels of DMI as compared to the levels of animals that had received DMI alone. These results evidence a stimulating effect of gangliosides on the development of adaptative receptor changes induced by chronic DMI treatment.
, with details of the nature of the infringement. We will investigate the claim and if justified,... more , with details of the nature of the infringement. We will investigate the claim and if justified, we will take the appropriate steps.
Psychiatry and Neuroscience Update - Vol. II, 2017
Stress is a major risk factor in the etiology of several psychiatric diseases, such as anxiety di... more Stress is a major risk factor in the etiology of several psychiatric diseases, such as anxiety disorders and depression. On the other hand, a growing body of evidence has demonstrated that astrocytes play a pivotal role in the normal functioning of the nervous system. Hence, understanding the effects of stress on astrocytes is crucial for a better comprehension of stress-related mental disorders. Here, we describe the evidence showing astrocyte changes induced by stress in animals and how this plasticity could operate to induce behavioral sequelae. In addition, human data linking astrocytes with psychiatric disorders related to stress are also discussed. Altogether, the data indicate that both chronic and acute stressors are capable of changing the morphology and function of astrocytes in the brain areas that are known to play a critical role in emotional processing, such as the prefrontal cortex, hippocampus, and amygdala. Furthermore, different lines of evidence suggest that astrocyte plasticity may contribute to the behavioral consequences of stress.
The destabilization/reconsolidation process can be triggered by memory recall, allowing consolida... more The destabilization/reconsolidation process can be triggered by memory recall, allowing consolidated memories to be modified. We have previously reported that stress prior to fear conditioning induces memories that exhibit resistance to the engagement of some molecular events associated with the destabilization/reconsolidation process. Here, we evaluated whether stress could affect the expression of Lys-48 polyubiquitinated proteins within the basolateral amygdala complex, a phenomenon crucially linked to memory destabilization. As expected, a post-recall increase of Lys-48 polyubiquitinated proteins in control animals was observed; however, this phenomenon was prevented by stress exposure before fear conditioning. On the other hand, pre-recall administration of D-cycloserine -a positive modulator of NMDA sites capable of reverting memory resistance to pharmacological interference-, facilitated the increase of Lys-48 polyubiquitinated proteins in stressed animals. In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to furthercharacterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling,protein degradation and memory destabilization in stress-induced resistant memories.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fear extinction is defined as a decline in fear-conditioned responses following non-reinforced ex... more Fear extinction is defined as a decline in fear-conditioned responses following non-reinforced exposure to a fear conditioned stimulus, therefore the conditioned stimulus gains new predictive properties. Patients with anxiety related disorders (e.g.: PTSD) subjected to extinction-like exposure treatments often experience a relapse of symptoms. Stress is a risk factor for those psychiatric disorders and a critical modulator of fear learning that turns the memory resistant to the extinction process. Dendritic spines are the anatomical sites where neuronal activity reshapes brain networks during learning and memory processes. Thus, we planned to characterize the dynamics of synaptic remodeling before and after contextual fear extinction in the dorsal hippocampus (DH), and how this process is affected by a previous stress experience. Animals with or without previous stress were contextually fear conditioned and one day later trained in an extinction paradigm. Rats were sacrificed one da...
Methods and findings in experimental and clinical pharmacology, 1992
The inclusion of clonidine (CLO) induced a dose-dependent reduction of K(+)-evoked [3H] dopamine ... more The inclusion of clonidine (CLO) induced a dose-dependent reduction of K(+)-evoked [3H] dopamine ([3H]DA) release in slices from rat nucleus accumbens. This inhibition was clearly attenuated in animals previously administered desipramine daily (DMI, 10 mg/kg i.p.) during 21 days, but not in rats submitted to a persistent treatment with DMI during 10 days. However, the coadministration of adrenocorticotrophic hormone (ACTH, 50 IU/kg s.c.) and DMI (10 mg/kg i.p.) for 10 days provoked a clear decrease in the inhibition produced by alpha 2-adrenoceptor stimulation, while ACTH alone had no effect. These results may indicate that ACTH accelerates the onset of DMI-induced adaptive changes on central alpha 2-adrenoceptor in the mesolimbic area.
The idea that memories are not invariable after the consolidation process has led to new perspect... more The idea that memories are not invariable after the consolidation process has led to new perspectives about several mnemonic processes. In this framework, we review our studies on the modulation of memory expression during reconsolidation. We propose that during both memory consolidation and reconsolidation, neuromodulators can determine the probability of the memory trace to guide behavior, i.e. they can either increase or decrease its behavioral expressibility without affecting the potential of persistent memories to be activated and become labile. Our hypothesis is based on the findings that positive modulation of memory expression during reconsolidation occurs even if memories are behaviorally unexpressed. This review discusses the original approach taken in the studies of the crab Neohelice (Chasmagnathus) granulata, which was then successfully applied to test the hypothesis in rodent fear memory. Data presented offers a new way of thinking about both weak trainings and experimental amnesia: memory retrieval can be dissociated from memory expression. Furthermore, the strategy presented here allowed us to show in human declarative memory that the periods in which long-term memory can be activated and become labile during reconsolidation exceeds the periods in which that memory is expressed, providing direct evidence that conscious access to memory is not needed for reconsolidation. Specific controls based on the constraints of reminders to trigger reconsolidation allow us to distinguish between obliterated and unexpressed but activated long-term memories after amnesic treatments, weak trainings and forgetting. In the hypothesis discussed, memory expressibility--the outcome of experience-dependent changes in the potential to behave--is considered as a flexible and modulable attribute of long-term memories. Expression seems to be just one of the possible fates of re-activated memories.
The modulatory effect of conditioned opiate analgesia on immobility during a forced swim situatio... more The modulatory effect of conditioned opiate analgesia on immobility during a forced swim situation was studied. Animals submitted to inescapable shock (IS) were exposed 6 days later to a similar or different shock application context and, immediately after, tested in either hot plate test or forced swim test. A conditioned analgesia was observed only on animals submitted to the shock context. This conditioned analgesia was blocked by naloxone administration injected either before IS or before context exposure. In the same way, animals exposed to shock context and immediately forced to swim showed an increase in the immobility time, which was sensitive to naloxone injection before IS as well as before context exposure. These results and additional data referring to naloxone effect on inactivity during IS are discussed in terms of the possible role of endogenous opiate in analogous behavior expressed during different aversive experiences.
Escape performance in a shuttie-box task was evaluated in rats chronically exposed to a series of... more Escape performance in a shuttie-box task was evaluated in rats chronically exposed to a series of unpredictable stressors either during 14 or 7 consecutive days. Failure in escape responses was observed when animals were subjected to both regimes of variable aversive situations. The association between chronic exposure to unpredictable stressors with imipramine resulted in a significant reversal of escape deficits. Furthermore, animals submitted to repeated immobilization sessions during 7 days presented similar escape response to control rats. A possible involvement of beta-adrenergic sites on this behavioral response is discussed. Shuttle-box Escape deficit Chronic variable stress Imipramine
Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. Th... more Cognitive dysfunction is one of the most severe nonmotor symptoms of nigrostriatal impairment. This occurs as a result of profound functional and morphological changes of different neuronal circuits, including modifications in the plasticity and architecture of hippocampal synapses. Such alterations can be implicated in the genesis and progression of dementia associated with neurodegenerative diseases including Parkinson-like symptoms. There are few studies regarding cognitive changes in nigrostriatal animal models. The aim of this study was to characterize the onset of memory deficit after induction of neurotoxicity with 6-hydroxydopamine (6-OHDA) and its correlation with hippocampal dysfunction. For this, we bilaterally microinjected 6-OHDA in dorsolateral Caudate-Putamen unit (CPu) and then, animals were tested weekly for working memory, spatial short-term memory, and motor performance. We evaluated tyrosine hydroxylase (TH) as a dopamine marker, aldehyde dehydrogenase 2 (ALDH2),...
It is known that a consolidated memory can return to a labile state and become transiently mallea... more It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiologica...
The present research was conducted to evaluate the influence of different stress schedules on beh... more The present research was conducted to evaluate the influence of different stress schedules on behaviors displayed during both phases of the forced swim test (FST). In addition, the involvement of an opiate mechanism in the behavioral consequences of chronic restraint was investigated. Exposure to a single, but not to chronic, restraint event induced an increase in the immobility score obtained during the 10-min initial swimming exposure (initial test) of the FST. Animals submitted to a previous regime of repeated restraint showed a significant increase in immobility during the 5-min second swimming exposure (retest period) of this behavioral task. However, naloxone (NAL) administered before each of the seven restraint events, blocked the higher immobility observed in chronically stressed rats during the retest period suggesting the involvement of an opiate mechanism. Results concerning the effect of chronic stress on the behavior displayed during the FST were discussed with reference to previous reports which have proposed that immobility performed during the retest period of the FST represents an efficient adaptive response in this inescapable aversive experience.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation.
In agreement with previous reports, low doses of apomorphine (10-50 micrograms/kg, 5 min before t... more In agreement with previous reports, low doses of apomorphine (10-50 micrograms/kg, 5 min before test) produced a dose-dependent decrease in motor activity of control rats. This effect was markedly attenuated 24 h after a prolonged immobilization stress (2 h daily during 7 days). A single stress session had no effect on motor activity. These behavioral observations suggest a reduced sensitivity of presynaptic dopamine receptors after chronic stress.
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