Papers by KARINA POSSA ABRAHÃO
A sensibilização comportamental ao efeito estimulante do etanol é caracterizada I pelo progressiv... more A sensibilização comportamental ao efeito estimulante do etanol é caracterizada I pelo progressivo aumento da atividade locomotora observada com a repetida I administração de uma mesma dose da droga. Atualmente, está sendo bastante estudado o envolvimento do sistema opioidérgico endógeno no alcoolismo e na dependência de outras drogas. Alguns estudos sugerem que o sistema opioidérgico modula a sensibilização comportamental ao etanol. No entanto, a sensibilização não ocorre de maneira homogênea para todas as espécies e nem mesmo para todos os indivíduos de uma mesma espécie. Dessa maneira, o objetivo geral desse estudo foi avaliar se o sistema opioidérgico influencia a expressão da atividade locomotora de animais que diferem quanto o nível de sensibilização comportamental ao efeito estimulante do etanol. Em todos os experimentos, camundongos Suíços albinos foram tratados durante 10 dias, recebendo 2,2g/kg de etanol (ip) ou salina, em dias alternados, sendo nestas ocasiões submetidos ...
bioRxiv (Cold Spring Harbor Laboratory), Jul 22, 2022
P/Q-type are the predominant VGCC controlling presynaptic Ca 2+ and GABA release on the striatal ... more P/Q-type are the predominant VGCC controlling presynaptic Ca 2+ and GABA release on the striatal indirect pathway projections GABAB receptor modulate of iSPN-GPe projections via a VGCC-dependent mechanism CB1 receptors modulate iSPN-GPe projections via a VGCC-independent mechanism
The Journal of Physiology, Dec 8, 2022
Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indire... more Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indirect pathway projections originate from A2A‐expressing spiny projection neurons (iSPNs), targeting the globus pallidus external segment (GPe) and control the firing of the tonically active GPe neurons via GABA release. It is unclear if and how the presynaptic G‐protein‐coupled receptors (GPCRs), GABAB and CB1 receptors modulate iSPN‐GPe projections. Here we used an optogenetic platform to study presynaptic Ca2+ and GABAergic transmission at iSPN projections, using a genetic strategy to express the calcium sensor GCaMP6f or the excitatory channelrhodopsin (hChR2) on iSPNs. We found that P/Q‐type calcium channels are the primary voltage‐gated Ca2+ channel (VGCC) subtype controlling presynaptic calcium and GABA release at iSPN‐GPe projections. N‐type and L‐type VGCCs also contribute to GABA release at iSPN‐GPe synapses. GABAB receptor activation resulted in a reversible inhibition of presynaptic Ca2+ transients (PreCaTs) and an inhibition of GABAergic transmission at iSPN‐GPe synapses. CB1 receptor activation did not inhibit PreCaTs but inhibited GABAergic transmission at iSPN‐GPe projections. CB1 effects on GABAergic transmission persisted in experiments where NaV and KV1 were blocked, indicating a VGCC‐ and KV1‐independent presynaptic mechanism of action of CB1 receptors. Taken together, presynaptic modulation of iSPN‐GPe projections by CB1 and GABAB receptors is mediated by distinct mechanisms. imageKey points P/Q‐type are the predominant voltage‐gated Ca2+ channels controlling presynaptic Ca2+ and GABA release on the striatal indirect pathway projections. GABAB receptors modulate iSPN‐GPe projections via a VGCC‐dependent mechanism. CB1 receptors modulate iSPN‐GPe projections via a VGCC‐independent mechanism.
Neuropharmacology, Mar 1, 2020
Alcohol is commonly used as a sleep inducer/aid by humans. However, individuals diagnosed with al... more Alcohol is commonly used as a sleep inducer/aid by humans. However, individuals diagnosed with alcohol use disorders have sleep problems. Few studies have examined the effect of ethanol on physiological features of sedation and anesthesia, particularly at high doses. This study used polysomnography and a rapid, unbiased scoring of vigilance states with an automated algorithm to provide a thorough characterization of dose-dependent acute ethanol effects on sleep and electroencephalogram (EEG) power spectra in C57BL/6J male mice. Ethanol had a narrow dose-response effect on sleep. Only a high dose (4.0 g/kg) dose produced a unique, transient state that could not be characterized in terms of canonical sleep-wake states, so we dubbed this novel state Drug-Induced State with a Characteristic Oscillation in the Theta Band (DISCO-T). After this anesthetic effect, the high dose of alcohol promoted NREM sleep by increasing the duration of NREM bouts while reducing wake. REM sleep was differentially responsive to the circadian timing of ethanol administration. EEG power spectra proved more sensitive to ethanol than sleep measures as there were clear effects of ethanol at 2.0 and 4.0 g/kg doses. Ethanol promoted delta oscillations and suppressed faster frequencies, but there were clear, differential effects on wake and REM EEG power based on the timing of the ethanol injection. Understanding the neural basis of the extreme soporific effects of high dose ethanol may aid in treating acute toxicity brought about by patterns of excessive binge consumption commonly observed in young people.
Neuropsychopharmacology, Nov 9, 2016
The Journal of Physiology, Jul 30, 2018
Classifying different subtypes of neurons in deep brain structures is a challenge and is crucial ... more Classifying different subtypes of neurons in deep brain structures is a challenge and is crucial to better understanding brain function.-Understanding the diversity of neurons in the Globus Pallidus, a brain region positioned to influence afferent and efferent information processing within basal ganglia, could help to explain a variety of brain functions.-We present a classification of neurons from the GP using electrophysiological data from wild type mice and confirmation using transgenic mice.-This work will help researchers to identify specific neuronal subsets in the GP of wild-type mice when transgenic mice with labeled neurons are lacking.
Trends in Neuroscience and Education, 2014
The use of neuroscience to improve education has been considered by researchers and practitioners... more The use of neuroscience to improve education has been considered by researchers and practitioners alike. However, workable solutions that lead to improvements in research and practice are yet to emerge. As newly qualified educational neuroscientists, our experiences dictate that the progress in this field relies upon 'Educational Neuroscience' being recognised as a distinct discipline. We therefore present a four-stage practical approach that concretely describes the role of the educational neuroscientist and details how neuroscientific knowledge can be practically assessed in the classroom. Using this approach, junior scientists will become empowered to replace the 'bridge' between education and neuroscience with a stronger, distinct Educational Neuroscience highway that is built in parallel to the existing paths.
IBRO neuroscience reports, Dec 1, 2023
ENeuro, Jul 1, 2022
Drinking behavior has been used in fundamental research to study metabolism, motivation, decision... more Drinking behavior has been used in fundamental research to study metabolism, motivation, decision-making and different aspects of health problems, such as anhedonia and alcohol use disorders. In the majority of studies, liquid intake is measured by weighing the bottles before and after the experiment. This method does not tell much about the drinking microstructure, e.g., licking bouts and periods of preference for each liquid, which could be valuable to understand drinking behavior. To improve data acquisition of drinking microstructure, companies have developed lickometer devices that acquire timestamps when animals approach or drink from a specific sipper. Nevertheless, commercially available devices have elevated costs. Here, we present a low-cost alternative for a lickometer system that allows wireless data acquisition of licks from eight cages with two sippers each. We ran a three-phase validation protocol to ensure (1) proper choice of the sensor to detect licks; (2) adaptation of the device to a wireless transmission and realistic in silico tests; and (3) in vivo validation to test the correlation between the amount of licks measured by the lickometer and the bottle weight. The capacitive sensor presented appropriate recall and precision for our device. After adaptation to wireless transmission, the in silico validation demonstrated low reading and transmission errors even when tested in extreme simultaneous licking conditions. Finally, we observed a positive correlation between water or ethanol consumption and lick count, showing that the lickometers can be used for in vivo studies interested in rodent drinking microstructure.
Alcoholism: Clinical and Experimental Research, Nov 25, 2021
Standard laboratory diets used have similar concentrations of proteins, carbohydrates and fat, bu... more Standard laboratory diets used have similar concentrations of proteins, carbohydrates and fat, but the concentration of some micronutrients can vary considerably. For example, the concentration of isoflavones can vary between 20 mg and 600 mg per gram of diet. Exposure to different concentrations of isoflavones interacts with alcohol (EtOH) intake, thereby influencing the results of alcohol research. In this mini‐review, we describe correlations between isoflavone concentrations and alcohol intake based on data from previously published work. Although the administration of low doses of isoflavones can decrease alcohol intake in rats, there is a positive correlation between the isoflavone content in diets and alcohol intake in mice. This interaction seems to depend on the dose, route of administration, and time of exposure to isoflavones and may be related to specific neurobiological mechanisms. The literature also indicates that isoflavones can interact with some of alcohol's molecular targets and with neural pathways crucial to the alcohol reward process. Given these findings, more attention should be given to the different types of laboratory diets used in alcohol studies to allow better comparison and replication of animal research.
O consumo de alcool pode aumentar o risco de acidentes de trânsito, mas a educacao sobre seus efe... more O consumo de alcool pode aumentar o risco de acidentes de trânsito, mas a educacao sobre seus efeitos pode promover reflexao quanto a evitar dirigir apos seu consumo. Objetiva-se relatar os resultados de uma acao extensionista na Semana Nacional de Ciencia e Tecnologia (2017). O foco foi explicar para criancas e adolescentes os efeitos do alcool no organismo por meio de posteres informativos e as estatisticas dos acidentes com motoristas alcoolizados. Em seguida, os visitantes eram convidados a uma dinâmica de simulacao de trânsito e dos perigos de beber antes de dirigir com os oculos simulador de embriaguez da 3B Scientific®. Como resultado, cerca de 110 visitantes interagiram no estande. Dentre os participantes, 98% deles responderam que “amaram” a dinâmica e 2% relataram que “gostaram”. Espera-se que esse estande seja levado para outras escolas para auxiliar esse na educacao sobre os efeitos do alcool de forma dinâmica e interativa. Palavras-chave: popularizacao da ciencia, exte...
Neuroscience, Aug 1, 2011
Behavioral sensitization to the stimulating effect of ethanol (EtOH) or other drugs, which can be... more Behavioral sensitization to the stimulating effect of ethanol (EtOH) or other drugs, which can be observed in mice as an increase in locomotor activity after repeated administration, has been associated with neuroadaptations within the dopaminergic mesolimbic pathway. In the nucleus accumbens (NAc), an afferent region of the mesolimbic pathway, dopamine (DA) release can be modulated by serotonergic 2C receptors (5-HT2C R). The aim of the present study was to evaluate the function of 5-HT2C R in the expression of EtOH-induced behavioral sensitization in Albino Swiss mice with various levels of sensitization to EtOH. In the four experiments that we performed, the mice were given saline or 2.2 g/kg EtOH daily for 21 days. Based on their locomotion on day 21, the EtOH-pretreated mice were assigned to one of two groups, highly sensitized or weakly sensitized to the stimulating effect of EtOH. In each experiment, 2 weeks after the 21-day treatment (withdrawal period), the mice were submitted to four pharmacological challenges of two drug treatments each. The mice in experiments 1 and 2 received two i.p. injections, whereas the mice in experiments 3 and 4 received an intra-NAc administration followed by an i.p. injection. The challenges were: saline؉saline; saline؉EtOH; SB-242084 (a 5-HT2C R antagonist; 0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 g/side intra-NAc)؉EtOH; and SB-242084 (0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 g/side intra-NAc)؉saline. At all tested doses, i.p. administration of SB-242084 did not affect the stimulating effect of EtOH in the highly sensitized mice. However, when delivered by intra-NAc administration, SB-242084 reduced (at 1.0 g/side) or completely blocked (at 2.0 g/ side) the expression of EtOH-induced behavioral sensitization in the highly sensitized mice. These findings suggest that the expression of behavioral sensitization to the stimulating effect of EtOH depends on accumbal 5-HT2C R activity.
Learning & Memory, Aug 16, 2018
Alcohol use disorders include drinking problems that span a range from binge drinking to alcohol ... more Alcohol use disorders include drinking problems that span a range from binge drinking to alcohol abuse and dependence. Plastic changes in synaptic efficacy, such as long-term depression and long-term potentiation are widely recognized as mechanisms involved in learning and memory, responses to drugs of abuse, and addiction. In this review, we focus on the effects of chronic ethanol (EtOH) exposure on the induction of synaptic plasticity in different brain regions. We also review findings indicating that synaptic plasticity occurs in vivo during EtOH exposure, with a focus on ex vivo electrophysiological indices of plasticity. Evidence for effects of EtOH-induced or altered synaptic plasticity on learning and memory and EtOH-related behaviors is also reviewed. As this review indicates, there is much work needed to provide more information about the molecular, cellular, circuit, and behavioral consequences of EtOH interactions with synaptic plasticity mechanisms.
PLOS ONE, Jan 20, 2017
Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies ... more Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress.
Frontiers in Behavioral Neuroscience, Mar 2, 2023
Neuropsychopharmacology
Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studie... more Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late ...
Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studie... more Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during ...
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Papers by KARINA POSSA ABRAHÃO