RESUMO
Ghrelin (Gr) is an orexigenic peptide that acts via its specific receptor, GHSR-1a distributed throughout the brain, being mainly enriched in pituitary, cortex and hippocampus (Hp) modulating a variety of brain functions. Behavioral, electrophysiological and biochemical evidence indicated that Gr modulates the excitability and the synaptic plasticity in Hp. The present experiments were designed in order to extend the knowledge about the Gr effect upon structural synaptic plasticity since morphological and quantitative changes in spine density after Gr administration were analyzed "in vitro" and "in vivo". The results show that Gr administered to hippocampal cultures or stereotactically injected in vivo to Thy-1 mice increases the density of dendritic spines (DS) being the mushroom type highly increased in secondary and tertiary extensions. Spines classified as thin type were increased particularly in primary extensions. Furthermore, we show that Gr enhances selectively the expression of BDNF-mRNA species.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Grelina/farmacologia , Hipocampo/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Hipocampo/citologia , Hipocampo/metabolismo , Microscopia Confocal , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células Piramidais/metabolismo , Células Piramidais/patologia , RNA Mensageiro/metabolismo , RatosRESUMO
Ghrelin (Grh) is an endogenous ligand of the growth hormone secretagogue receptor. In neonatal chicks, central Ghr induces anxiogenic-like behavior but strongly inhibits food intake. The intermediate medial mesopallium (IMM) of the chick forebrain has been identified to be a site of the memory formation, and the modulation of the GABAA receptors that are present here modifies the expression of behavior. Thus, the GABAergic system may constitute a central pathway for Ghr action in regulating the processes of food intake and stress-related behaviors. Therefore, we investigated if the effect of systemic administration of bicuculline (GABAA receptor antagonist) and diazepam (benzodiazepine receptor agonist) on the anxiety in an Open Field test and inhibition in food intake induced by Grh (30pmol) when injected into IMM, were mediated by GABAergic transmission. In Open Field test, bicuculline was able to block the anxiogenic-like behavior induced by Ghr, whereas diazepam did not produce it. However, the co-administration of bicuculline or diazepam plus Ghr did not show any change in food intake at 30, 60 and 120min after injection compared to Ghr alone. Our results indicate for the first time that Ghr, injected into the forebrain IMM area, induces an anxiogenic-like behavior, which was blocked by bicuculline but not diazepam, thus suggesting that Ghr plays an important role in the response pattern to acute stressor, involving the possible participation of the GABAergic system. Nevertheless, as neither drug affected the hypophagia induced by intra-IMM Ghr, this suggests that it may be mediated by different mechanisms.
Assuntos
Ansiedade/metabolismo , Comportamento Animal/fisiologia , Cérebro/metabolismo , Ingestão de Alimentos/fisiologia , Grelina/fisiologia , Receptores de GABA-A/fisiologia , Animais , Animais Recém-Nascidos , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Cérebro/efeitos dos fármacos , Galinhas , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Grelina/administração & dosagem , Grelina/farmacologia , MasculinoRESUMO
A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/µl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/µl and 3.0 nmol/µl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/µl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity.
Assuntos
Ansiedade/metabolismo , Ingestão de Alimentos/fisiologia , Hipocampo/metabolismo , Memória/fisiologia , Fragmentos de Peptídeos/metabolismo , Somatostatina/metabolismo , Animais , Ingestão de Alimentos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
Hippocampus is a limbic structure that participates in learning and memory formation. Specifically the dentate gyrus has been described as a hippocampal subregion with high rates of plasticity and it is targeted by different psychoactive drugs modulating synaptic plasticity. Repeated cocaine administration induces sensitization to the locomotor effects and it is believed that sensitization involves the same mechanisms of drug seeking and relapse. Although, the mechanisms underlying sensitization is not fully understood. In this work we investigated the impact of repeated intraperitoneal administration of cocaine (15 or 20 mg/kg/day along 5 or 15 days respectively; and 15 mg/kg/day along 5 day followed by a challenge dose after three days of withdrawal) on the dentate gyrus synaptic plasticity, differentiating between sensitized and nonsensitized rats. Furthermore, we correlated changes on the hippocampal synaptic plasticity to memory retention. Our results revealed that the prevalence of cocaine sensitization (around 50%) was identical in all protocols used. The results found in the threshold to generate LTP were similar for all protocols used, being the threshold values cocaine-treated groups (sensitized and nonsensitized) significantly reduced compared to controls, observing the highest reduction in the sensitized group. Moreover, we observed a facilitated retention of recent memory formation only in sensitized animals the nonsensitized subjects remained at the control levels. In conclusion, sensitization to cocaine generates a high efficiency of hippocampal synaptic plasticity that may underlie the aberrant engagement of learning processes occurred during drug addiction.
Assuntos
Anestésicos Locais/efeitos adversos , Cocaína/efeitos adversos , Giro Denteado/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Biofísica , Distribuição de Qui-Quadrado , Relação Dose-Resposta a Droga , Esquema de Medicação , Estimulação Elétrica/métodos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Potenciação de Longa Duração/fisiologia , Masculino , Atividade Motora/fisiologia , Técnicas de Patch-Clamp , Desempenho Psicomotor/fisiologia , Ratos , Ratos Wistar , Estatística como AssuntoRESUMO
It has been demonstrated, in normal and aged rats and mice, that acute i.c.v. ghrelin (Ghr) administration increases memory retention. In order to evaluate if this treatment, restores memory retention in animals exhibiting impaired memory, in the present work we selected a chronic food restriction mouse model (since undernutrition prejudices higher nervous functions). We employed adult female mice with 28 days of 50% food restriction and evaluated: a) behavioral performance using novel object recognition test for memory, and plus maze for anxiety-like behavior, b) some morphometric parameters as body and hepatic weights and c) plasma Ghr levels. The animals with 50% food restriction showed an increase in plasma Ghr levels and a decrease in morphometric parameters and in the percentage of novel object recognition time. When the peptide was i.c.v. injected in food-restricted animals (0.03, 0.3 or 3.0 nmol/microl), memory increases in relation to food-restricted mice injected with vehicle, reaching a performance similar to controls.
Assuntos
Comportamento Exploratório/efeitos dos fármacos , Grelina/administração & dosagem , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Reconhecimento Psicológico/efeitos dos fármacos , Inanição/complicações , Análise de Variância , Animais , Comportamento Animal , Peso Corporal/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/fisiologia , Feminino , Grelina/sangue , Fígado/efeitos dos fármacos , Fígado/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/patologia , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/fisiologia , Fatores de TempoRESUMO
In this study, the involvement of nitric oxide (NO) in the mechanism of anxiety was investigated. The rats received an intraamygdaline or intrahippocampal injection of the nitric oxide synthase inhibitor, N(G)-nitro-l-arginine (L-NOARG), and were then tested in the plus-maze test. L-NOARG induced a decrease in the time spent by rats in the open arms. Conversely, the administration of the melanin-concentrating hormone (MCH) into these structures increased the number of entries into the open arms as well as the time spent on them. MCH injected in rats pretreated with L-NOARG also was able to revert the anxiogenic effects of L-NOARG in amygdala.
Assuntos
Encéfalo/enzimologia , Inibidores Enzimáticos/farmacologia , Hormônios Hipotalâmicos/farmacologia , Melaninas/farmacologia , Neovascularização Patológica , Óxido Nítrico Sintase/antagonistas & inibidores , Oxigênio/metabolismo , Hormônios Hipofisários/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/enzimologia , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Óxido Nítrico/metabolismo , Nitroarginina/farmacologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The interaction between the neuropeptide alpha-MSH and the acetylcholinergic system as reflected by changes in cAMP and inositol 1-3-5 triphosphate(IP(3))production was investigated in an in vitro model of striatal slices. The possible involvement of D(1) receptors in cholinergic and alpha-MSH- stimulated cAMP and IP(3) production in slices of rat striatum was also examined, because it has been demonstrated that acetylcholinergic drugs induce endogenous dopamine release in the striatum. alpha-MSH, pilocarpine(PL) and the selective muscarinic M1 agonist McN-A-343 increased cAMP and IP(3) striatal levels, effects blocked by the D(1) antagonist SCH-23390, except for the effects of alpha-MSH on IP(3). The muscarinic M(2) antagonist gallamine (GL) brought about an increase in cAMP levels, an effect blocked by SCH-23390. The M(1) antagonist pirenzepine (Pz) induced a decrease both in cAMP and IP(3) content, and the nicotinic antagonist di-hydro-beta-eritroidine(DBE) only diminished cAMP production. When alpha-MSH and cholinergic agents were simultaneously added, cAMP and IP(3) levels were modified with respect to the values reached when these agents were added alone. An interaction between the acetylcholinergic system and alpha-MSH through M(1) and nicotinic receptors was also observed. These results suggest that the intracellular signaling pathways related to cAMP and IP(3) production gated by alpha-MSH and these cholinergic receptors are probably related. alpha-MSH striatum cAMP IP(3) muscarinic and nicotinic receptors an in vitro model.
Assuntos
Acetilcolina/metabolismo , Corpo Estriado/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Receptores Colinérgicos/metabolismo , alfa-MSH/metabolismo , Animais , Inositol 1,4,5-Trifosfato/biossíntese , Masculino , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Ratos , Ratos Wistar , Receptores Colinérgicos/efeitos dos fármacosRESUMO
Some behavioral response of rats to spatial novelty after i.c.v. administration of melanin-concentrating hormone (MCH) were evaluated. To this purpose, an open-field test was used, as well as an elevated plus-maze to study the possible anxiolytic effect of this peptide. In the open field, the frequency of exploratory components (locomotion and rearing) increased after MCH administration in comparison to controls. Moreover, in the plus-maze, MCH increased the number of entries into the open arms as well as the time spent on them, whereas no changes in the number of entries onto the closed arms were found. The data indicate that MCH exerts an anxiolytic effect, and suggests a physiological role for this.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Meio Ambiente , Hormônios Hipotalâmicos/farmacologia , Melaninas/farmacologia , Hormônios Hipofisários/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/psicologia , Comportamento Exploratório/efeitos dos fármacos , Hormônios Hipotalâmicos/administração & dosagem , Injeções Intraventriculares , Masculino , Melaninas/administração & dosagem , Atividade Motora/efeitos dos fármacos , Periodicidade , Hormônios Hipofisários/administração & dosagem , Ratos , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologiaRESUMO
The purpose of the present study was to evaluate the possible effect of melanin-concentrating hormone (MCH) on learning and memory by using the one-trial step-down inhibitory avoidance test in rats. The peptide was infused into hippocampus, amygdala, and entorhinal cortex. MCH caused retrograde facilitation when given at 0 or 4 h post-training into hippocampus, but only at 0 h into amygdala. From these results, it seems that MCH modulates memory early after training by acting on both the amygdala and hippocampus and, 4 h after training, on the hippocampus.
Assuntos
Hormônios Hipotalâmicos/farmacologia , Melaninas/farmacologia , Memória/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Hormônios Hipotalâmicos/administração & dosagem , Masculino , Melaninas/administração & dosagem , Memória/fisiologia , Hormônios Hipofisários/administração & dosagem , Ratos , Ratos Wistar , Fatores de TempoRESUMO
We have tried to investigate the possible interaction between the gabaergic system and alpha-MSH at a cellular level in an in vitro model of male albino rats tissue slices containing accumbens and caudate-putamen nuclei. Alpha-MSH alone increases cAMP levels, as does diazepam and phaclofen; however, these effects were blocked by SCH-23390. Both flumazenil and baclofen induced a decrease in the cAMP content. When both alpha-MSH and gabaergic agents were incubated together, cAMP levels were modified. It can be assumed that cAMP production by the neuropeptide and the gabaergic agents could be linked to the activation of dopaminergic D1 receptors. The latter receptors had no prominent effect on the interaction between alpha-MSH and the GABA agonists and antagonists. In summary, our results suggested that alpha-MSH and GABA system could be biochemically linked to produce a cellular effect.