RESUMO
The present study was done to determine whether cannabinoid CB1 receptors of the central amygdala (CeA) are implicated in morphine-induced place preference. Using a 3-day schedule of conditioning, it was found that subcutaneous (s.c.) administration of morphine (2, 4 and 6 mg/kg) caused a significant dose-dependent conditioned place preference (CPP) in male Wistar rats. Intra-CeA microinjection of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA; 0.5, 2.5 and 5 ng/rat) dose-dependently potentiated the morphine (2mg/kg)-induced CPP. Furthermore, the administration of ACPA (5 ng/rat, intra-CeA) alone induced a significant CPP. It should be considered that the higher dose of ACPA (5 ng/rat, intra-CeA) in combination with morphine decreased locomotor activity on the testing phase. On the other hand, intra-CeA microinjection of the cannabinoid CB1 receptor antagonist AM251 (120 ng/rat) alone induced a significant conditioned place aversion (CPA). Moreover, intra-CeA microinjection of AM251 (90 and 120 ng/rat) inhibited the morphine-induced place preference with a significant interaction. Intra-CeA microinjection of AM251 reversed the effect of ACPA on morphine response. Interestingly, microinjection of ACPA (2.5 and 5 ng/rat) or AM251 (60-120 ng/rat) into the CeA increased or decreased the expression of morphine (6 mg/kg)-induced place preference respectively. These observations provide evidence that cannabinoid CB1 receptors of the CeA are involved in mediating reward and these receptors are also implicated in the acquisition and expression of morphine-induced CPP.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Condicionamento Operante/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Análise de Variância , Animais , Ácidos Araquidônicos/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , Atividade Motora/efeitos dos fármacos , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Esquema de ReforçoRESUMO
The possible involvement of N-methyl-D-aspartate (NMDA) receptors of the nucleus accumbens (NAc) in amnesia induced by scopolamine was investigated. An inhibitory (passive) avoidance task was used for memory assessment in male Wistar rats. The results revealed that intra-NAc administration of a nonselective muscarinic acetylcholine antagonist, scopolamine (1 and 2 g/rat) impaired memory consolidation in the animals when tested 24 h later. Post-training intra-NAc administration of NMDA (0.005 and 0.01 g/rat) also impaired memory consolidation, whereas post-training intra-NAc administration of the NMDA receptor antagonist, MK-801 (0.5, 1 and 1.5 g/rat) did not. Intra-NAc co-administration of an ineffective dose of NMDA with ineffective doses of scopolamine (0.25 and 0.5 g/rat) after training had no significant effect on memory consolidation, but intra-NAc injections of effective doses of NMDA (0.005 and 0.01 g/rat) prevented the amnesic effect of an effective dose of scopolamine (2 g/rat). In contrast, intra-NAc co-administration of MK-801 (0.5, 1 and 1.5 g/rat) along with an effective dose of scopolamine (2 g/rat) did not prevent the effect of the latter drug. It can be concluded that NMDA receptors in the NAc are involved in the modulation of memory consolidation that was affected by scopolamine.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas Colinérgicos/toxicidade , Ácido Glutâmico/metabolismo , Transtornos da Memória/induzido quimicamente , Núcleo Accumbens/efeitos dos fármacos , Escopolamina/toxicidade , Animais , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Inibição Psicológica , Masculino , Microinjeções , N-Metilaspartato/farmacologia , Núcleo Accumbens/metabolismo , Ratos , Ratos WistarRESUMO
The possible role of ventral hippocampal N-methyl-d-aspartate (NMDA) receptors on morphine-induced anxiolytic-like behavior in an elevated plus maze (EPM) task was investigated in the present study. Adult male mice (7 per group) with cannulas aimed at the ventral hippocampus (VH) received NMDA or a competitive NMDA receptor antagonist D-AP5 with or without morphine and 30min later were subjected to an EPM task. Intraperitoneal injection (i.p.) of morphine (3-9mg/kg) increased the percentage of open arm time (%OAT) and open arm entries (%OAE), which suggested an anxiolytic-like effect. Intra-VH microinjection of NMDA (0.5-1µg/mouse) with an ineffective dose of morphine (3mg/kg, i.p.) significantly increased %OAT and %OAE. However, microinjections of the same doses of NMDA into the VH in the absence of morphine had no effect on %OAT and %OAE. Intra-VH microinjection of D-AP5 (0.5-2µg/mouse) decreased the anxiolytic-like effect of morphine, while intra-VH microinjection of the same doses of D-AP5 alone increased %OAT and %OAE, which indicated an anxiolytic response. Furthermore, intra-VH microinjection of D-AP5 reversed the effect of NMDA response to the administration of a lower morphine dose as seen in the EPM task. It should be noted that intra-VH microinjection of D-AP5 plus NMDA, 5min before morphine increased locomotor activity, while other treatments had no effect on this parameter. The results suggest that VH-NMDA receptors participate in the mediation of morphine-induced anxiolytic-like behavior.
Assuntos
Ansiedade/tratamento farmacológico , Hipocampo/fisiologia , Morfina/farmacologia , Morfina/uso terapêutico , Receptores de N-Metil-D-Aspartato/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , Análise de Variância , Animais , Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Camundongos , Microinjeções , Atividade Motora/efeitos dos fármacos , N-Metilaspartato/farmacologia , Entorpecentes/farmacologia , Entorpecentes/uso terapêuticoRESUMO
Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation.
Assuntos
Amnésia/induzido quimicamente , Aprendizagem da Esquiva/fisiologia , Harmina/análogos & derivados , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Amnésia/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Benzazepinas/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Harmina/toxicidade , Masculino , Camundongos , Projetos Piloto , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
AIMS: The current study was undertaken to determine the role of dorsal hippocampal N-methyl-d-aspartate (NMDA) receptors in nicotine's effect on impairment of memory by ethanol. MAIN METHODS: Adult male mice were cannulated in the CA1 regions of dorsal hippocampi and trained on a passive avoidance learning task for memory assessment. KEY FINDINGS: We found that pre-training intraperitoneal (i.p.) administration of ethanol (0.5 and 1g/kg) decreased memory retrieval when tested 24h later. Pre-test administration of ethanol reversed the decrease in inhibitory avoidance response induced by pre-training ethanol. Similar to ethanol, pre-test administration of nicotine (0.125-0.75 mg/kg, s.c.) prevented impairment of memory by pre-training ethanol. In the animals that received ethanol (1g/kg, i.p) before training and tested following intra-CA1 administration of different doses of NMDA (0.0005-0.005 microg/mouse), no significant change was observed in the retrieval latencies. Co-administration of the same doses of NMDA with an ineffective dose of nicotine (0.125 mg/kg, s.c.) significantly improved the memory retrieval and mimicked the effects of pre-test administration of a higher dose of nicotine. Pre-test intra-CA1 microinjection of MK-801 (0.25-1 microg/mouse), which had no effect alone, in combination with an effective dose of nicotine (0.75 mg/kg, s.c.) prevented the improving effect of nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1 microinjection of MK-801 reversed the NMDA-induced potentiation of the nicotine response. SIGNIFICANCE: The results suggest the importance of NMDA glutamate system(s) in the CA1 regions of dorsal hippocampus for improving the effect of nicotine on the ethanol-induced amnesia.