It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT n... more It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HTIA agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HTIA receptors located in the hippocampus participate in the development of tolerance to aver sive events.
Alcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively... more Alcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively sought for prevention and treatment. The orphan G protein-coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential role for this receptor in drug abuse has not been examined. We tested Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system-level understanding of their alcohol endophenotype, we also analyzed whole-brain functional connectivity in naïve mice using resting-state functional magnetic resonance imaging. Gpr88 knockout mice showed increased voluntary alcohol drinking at both moderate and excessive levels, with intact alcohol sedation and metabolism. Mutant mice also showed increased operant responding and motivation for alcohol, while food and chocolate operant self-administration were unchanged. Alcohol place conditioning and alcohol-induced dopamine release ...
High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail o... more High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail over caloric necessities leading to overeating and overweight. The nucleus accumbens (NAc) is a key brain area modulating the reinforcing effects of palatable foods and is crucially involved in the development of eating disorders. We describe that prolonged exposure to high-caloric chocolate cafeteria diet leads to overeating and overweight in mice. NAc functionality was altered in these mice, presenting structural plasticity modifications in medium spiny neurons, increased expression of neuroinflammatory factors and activated microglia, and abnormal responses after amphetamine-induced hyperlocomotion. Chronic inactivation of microglia normalized these neurobiological and behavioural alterations exclusively in mice exposed to cafeteria diet. Our data suggest that prolonged exposure to cafeteria diet produces neuroplastic and functional changes in the NAc that can modify feeding behaviour....
Several lines of evidence support that food overconsumption may be related to the role of the end... more Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genot...
RESUMO: "Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodi... more RESUMO: "Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodialis Eichler em roedores". A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modifi cou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.
RESUMO:"Avaliação do efeito ansiolítico de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocyn... more RESUMO:"Avaliação do efeito ansiolítico de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, nos testes do labirinto em cruz elevado e placa-perfurada". Rauvolfia ligustrina Willd. ex Roem. & Schult. (Apocynaceae) é conhecida popularmente como "arrebenta-boi" e "paratudo". Em triagem farmacológica comportamental o extrato etanólico das raízes de R. ligustrina (EER) mostrou efeito depressor do SNC e propriedades anticonvulsivantes. O presente estudo buscou avaliar o possível efeito ansiolítico do EER utilizando os testes do labirinto em cruz elevado (LCE) e o teste da placa perfurada ("hole-board") em roedores. A administração do EER, por via intraperitoneal (i.p.), em diferentes doses (3,9; 7,8 e 15,6 mg/kg) foi capaz de aumentar significativamente o número de entradas (p < 0,05), assim como o tempo despendido nos braços abertos do LCE. Além disso, nos animais tratados com o EER (3,9 e 7,8 mg/kg, i.p.) ocorreu aumento significativo no número de visitas à borda e mergulho com a cabeça no teste da placa perfurada em comparação com os animais do grupo controle. Estes dados sugerem um possível efeito ansiolítico do EER nos modelos animais testados.
Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of ... more Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of the inhalation of linalool oxide (0.65%, 1.25%, 2.5% and 5.0% w/w) in the elevated plus-maze and light/dark box tests as animal models of anxiety were investigated in adult male mice and compared with the effects of the reference anxiolytic diazepam (0.5 and 2.0 mg/kg), administered intraperitoneally. Additionally, the effects of inhaled linalool oxide were investigated in the rotarod test. Linalool oxide significantly increased the number of visits to the open arms of the elevated plus-maze and the amount of time spent there as well as the total number of entries. In the light/dark box test, inhalation of linalool oxide led to an increase in the time spent by the mice in the brightly-lit chamber and in the number of times the animal crossed from one compartment to another. Performance on the rotarod was unaffected. Thus, inhaled linalool oxide was found to have anxiolytic properties in ...
Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of... more Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of an elevated plus maze 24 h later. This effect was attenuated by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted with canulae in the dorsal hippocampus. Seven days later they received bilateral microinjections of 5-MeODMT (20 nmol/0.5/~1) or saline. No difference was found on exploration of an elevated plus maze 24 h later. However, when treatments were performed immediately after 2 h of restraint stress, the drug was able to increase open arm exploration 24 h later. This effect was antagonized by a previous microinjection of (+)WAY-100135 (40 nmol/0.5 #1), a selective 5-HT1A antagonist. The results suggest that hippocampal 5.-HT1A receptors may attenuate stress behavioral consequences.
Page 1. 1 Capítulo 11 (pag. 182-196), Publicado em: Santos, Franklin Santana (org). (2010). Arte ... more Page 1. 1 Capítulo 11 (pag. 182-196), Publicado em: Santos, Franklin Santana (org). (2010). Arte de Cuidar: Saúde, Espiritualidade e Educação. Bragança Paulista, SP; Editora Comenius. Metodologia de Pesquisa para Estudos em Espiritualidade e Saúde Sueli Mendonça Netto 1 e Alexander Moreira-Almeida 2 1 Graduada em Biologia pela Universidade Federal de Juiz de Fora, Doutora em Psicobiologia pela Faculdade de Ciência e Letras de Ribeirão Preto da Universidade ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2002
Serotonin (5-HT) neurons located in the median raphe nucleus (MRN) may have a role in the develop... more Serotonin (5-HT) neurons located in the median raphe nucleus (MRN) may have a role in the development of behavioral changes to stress. The objective of the present work was to investigate the effects of a selective lesion of 5-HT neurons located in the MRN in previously stressed male Wistar rats submitted to the elevated plus maze (EPM). In an initial experiment, the animals (n=20-22) were submitted to one (acute) or seven (chronic) daily restraint stress periods (2 h) and tested in the EPM 24 h later. Results showed that acute restraint caused a significant decrease in the number of entries into the open arms, as compared to nonstressed controls. This effect disappeared when the animals were submitted to chronic restraint. In the next set of experiments, animals (n=6-8) received, 1 week before the behavioral studies, intra-MRN injection of 5,7-dihydroxytryptamine (5,7-DHT; 8 mg/1 ml). Neurochemical analysis showed that this treatment significantly decreases 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) levels in the hippocampus, but not in the striatum. No difference between lesioned and sham-operated animals in EPM performance was found in nonstressed animals or in those submitted to acute restraint. In chronically restrained animals, however, lesioned rats showed a significant decrease in the number of entries and time spent in the open arms. These results suggest that lesions of 5-HT neurons located in the MRN cause anxiogenic-like behavior in animals that have been chronically restrained.
It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT n... more It has been suggested that postsynaptic 5-HT1A receptors in the hippocampus, innervated by 5-HT neurons localized in the median raphe nucleus, mediate adaptive or coping responses to aversive events and that dysfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in animals submitted to immobilization stress. The results showed that c-fos mRNA expression is significantly increased in the dentate gyrus and CA1-CA3 regions of the hippocampus after 30 min of forced restraint, suggesting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h later in an elevated plus-maze. Our results showed that the previous restraint period decreases exploration of open arms in the maze. This effect was reversed by bilateral microinjection of zimelidine (20 and 100 nmol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HTIA agonist, into the dorsal hippocampus immediately after restraint. These results are compatible with the idea that postsynaptic 5-HTIA receptors located in the hippocampus participate in the development of tolerance to aver sive events.
Alcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively... more Alcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively sought for prevention and treatment. The orphan G protein-coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential role for this receptor in drug abuse has not been examined. We tested Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system-level understanding of their alcohol endophenotype, we also analyzed whole-brain functional connectivity in naïve mice using resting-state functional magnetic resonance imaging. Gpr88 knockout mice showed increased voluntary alcohol drinking at both moderate and excessive levels, with intact alcohol sedation and metabolism. Mutant mice also showed increased operant responding and motivation for alcohol, while food and chocolate operant self-administration were unchanged. Alcohol place conditioning and alcohol-induced dopamine release ...
High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail o... more High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail over caloric necessities leading to overeating and overweight. The nucleus accumbens (NAc) is a key brain area modulating the reinforcing effects of palatable foods and is crucially involved in the development of eating disorders. We describe that prolonged exposure to high-caloric chocolate cafeteria diet leads to overeating and overweight in mice. NAc functionality was altered in these mice, presenting structural plasticity modifications in medium spiny neurons, increased expression of neuroinflammatory factors and activated microglia, and abnormal responses after amphetamine-induced hyperlocomotion. Chronic inactivation of microglia normalized these neurobiological and behavioural alterations exclusively in mice exposed to cafeteria diet. Our data suggest that prolonged exposure to cafeteria diet produces neuroplastic and functional changes in the NAc that can modify feeding behaviour....
Several lines of evidence support that food overconsumption may be related to the role of the end... more Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genot...
RESUMO: "Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodi... more RESUMO: "Efeitos antidepressivos da fração de alcalóides terciários totais de Cissampelos sympodialis Eichler em roedores". A proposta deste trabalho foi de avaliar os efeitos da fração de alcalóides terciários totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressão: a) teste do nado forçado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Também reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF não modifi cou a ambulação e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a redução no tempo de imobilidade apresentada no teste do nado forçado foi causada por estimulação na atividade locomotora. Como a warifteína é um dos principais alcalóides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsável pelo efeito antidepressivo observado na fração estudada.
RESUMO:"Avaliação do efeito ansiolítico de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocyn... more RESUMO:"Avaliação do efeito ansiolítico de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, nos testes do labirinto em cruz elevado e placa-perfurada". Rauvolfia ligustrina Willd. ex Roem. & Schult. (Apocynaceae) é conhecida popularmente como "arrebenta-boi" e "paratudo". Em triagem farmacológica comportamental o extrato etanólico das raízes de R. ligustrina (EER) mostrou efeito depressor do SNC e propriedades anticonvulsivantes. O presente estudo buscou avaliar o possível efeito ansiolítico do EER utilizando os testes do labirinto em cruz elevado (LCE) e o teste da placa perfurada ("hole-board") em roedores. A administração do EER, por via intraperitoneal (i.p.), em diferentes doses (3,9; 7,8 e 15,6 mg/kg) foi capaz de aumentar significativamente o número de entradas (p < 0,05), assim como o tempo despendido nos braços abertos do LCE. Além disso, nos animais tratados com o EER (3,9 e 7,8 mg/kg, i.p.) ocorreu aumento significativo no número de visitas à borda e mergulho com a cabeça no teste da placa perfurada em comparação com os animais do grupo controle. Estes dados sugerem um possível efeito ansiolítico do EER nos modelos animais testados.
Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of ... more Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of the inhalation of linalool oxide (0.65%, 1.25%, 2.5% and 5.0% w/w) in the elevated plus-maze and light/dark box tests as animal models of anxiety were investigated in adult male mice and compared with the effects of the reference anxiolytic diazepam (0.5 and 2.0 mg/kg), administered intraperitoneally. Additionally, the effects of inhaled linalool oxide were investigated in the rotarod test. Linalool oxide significantly increased the number of visits to the open arms of the elevated plus-maze and the amount of time spent there as well as the total number of entries. In the light/dark box test, inhalation of linalool oxide led to an increase in the time spent by the mice in the brightly-lit chamber and in the number of times the animal crossed from one compartment to another. Performance on the rotarod was unaffected. Thus, inhaled linalool oxide was found to have anxiolytic properties in ...
Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of... more Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of an elevated plus maze 24 h later. This effect was attenuated by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted with canulae in the dorsal hippocampus. Seven days later they received bilateral microinjections of 5-MeODMT (20 nmol/0.5/~1) or saline. No difference was found on exploration of an elevated plus maze 24 h later. However, when treatments were performed immediately after 2 h of restraint stress, the drug was able to increase open arm exploration 24 h later. This effect was antagonized by a previous microinjection of (+)WAY-100135 (40 nmol/0.5 #1), a selective 5-HT1A antagonist. The results suggest that hippocampal 5.-HT1A receptors may attenuate stress behavioral consequences.
Page 1. 1 Capítulo 11 (pag. 182-196), Publicado em: Santos, Franklin Santana (org). (2010). Arte ... more Page 1. 1 Capítulo 11 (pag. 182-196), Publicado em: Santos, Franklin Santana (org). (2010). Arte de Cuidar: Saúde, Espiritualidade e Educação. Bragança Paulista, SP; Editora Comenius. Metodologia de Pesquisa para Estudos em Espiritualidade e Saúde Sueli Mendonça Netto 1 e Alexander Moreira-Almeida 2 1 Graduada em Biologia pela Universidade Federal de Juiz de Fora, Doutora em Psicobiologia pela Faculdade de Ciência e Letras de Ribeirão Preto da Universidade ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2002
Serotonin (5-HT) neurons located in the median raphe nucleus (MRN) may have a role in the develop... more Serotonin (5-HT) neurons located in the median raphe nucleus (MRN) may have a role in the development of behavioral changes to stress. The objective of the present work was to investigate the effects of a selective lesion of 5-HT neurons located in the MRN in previously stressed male Wistar rats submitted to the elevated plus maze (EPM). In an initial experiment, the animals (n=20-22) were submitted to one (acute) or seven (chronic) daily restraint stress periods (2 h) and tested in the EPM 24 h later. Results showed that acute restraint caused a significant decrease in the number of entries into the open arms, as compared to nonstressed controls. This effect disappeared when the animals were submitted to chronic restraint. In the next set of experiments, animals (n=6-8) received, 1 week before the behavioral studies, intra-MRN injection of 5,7-dihydroxytryptamine (5,7-DHT; 8 mg/1 ml). Neurochemical analysis showed that this treatment significantly decreases 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) levels in the hippocampus, but not in the striatum. No difference between lesioned and sham-operated animals in EPM performance was found in nonstressed animals or in those submitted to acute restraint. In chronically restrained animals, however, lesioned rats showed a significant decrease in the number of entries and time spent in the open arms. These results suggest that lesions of 5-HT neurons located in the MRN cause anxiogenic-like behavior in animals that have been chronically restrained.
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