RESUMO
The aim of the present study was to investigate the possible role of basolateral amygdala (BLA) 5-HT1A receptors in memory formation under stress. We also examined whether the blockade of these receptors is involved in stress-induced state-dependent memory. Adult male Wistar rats received cannula implants that bilaterally targeted the BLA. Long-term memory was examined using the step-through type of passive avoidance task. Behavioral stress was evoked by exposure to an elevated platform (EP) for 10, 20 and 30min. Post-training exposure to acute stress (30min) impaired the memory consolidation. In addition, pre-test exposure to acute stress-(20 and 30min) induced the impairment of memory retrieval. Interestingly, the memory impairment induced by post-training exposure to stress was restored in the animals that received 20- or 30-min pre-test stress exposure, suggesting stress-induced state-dependent memory retrieval. Post-training BLA-targeted injection of a selective 5-HT1A receptor antagonist, (S)-WAY-100135 (2µg/rat), prevented the impairing effect of stress on memory consolidation. Pre-test injection of the same doses of (S)-WAY-100135 that was targeted to the BLA also reversed stress-induced memory retrieval impairment. It should be considered that post-training or pre-test BLA-targeted injection of (S)-WAY-100135 (0.5-2µg/rat) by itself had no effect on the memory formation. Moreover, pre-test injection of (S)-WAY-100135 (2µg/rat) that targeted the BLA inhibited the stress-induced state-dependent memory retrieval. Taken together, our findings suggest that post-training or pre-test exposure to acute stress induced the impairment of memory consolidation, retrieval and state-dependent learning. The BLA 5-HT1A receptors have a critical role in learning and memory under stress.
Assuntos
Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Piperazinas/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Estresse Psicológico/tratamento farmacológico , Doença Aguda , Animais , Complexo Nuclear Basolateral da Amígdala/fisiopatologia , Cateteres de Demora , Modelos Animais de Doenças , Masculino , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Transtornos da Memória/fisiopatologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Longo Prazo/fisiologia , Rememoração Mental/efeitos dos fármacos , Rememoração Mental/fisiologia , Ratos Wistar , Receptor 5-HT1A de Serotonina/metabolismo , Estresse Psicológico/fisiopatologiaRESUMO
The present study was designed to investigate possible involvement of the central amygdala (CeA) nicotinic acetylcholine (nACh) and 5-hydroxytryptamine 1A (5-HT1A) receptors in the reversal effect of nicotine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) on morphine-induced amnesia. Two guide cannulas were stereotaxically implanted in the CeA regions and a step-through passive avoidance task was used for the assessment of memory retrieval in adult male Wistar rats. Our results indicated that post-training s.c. administration of morphine (3-7-mg/kg) impaired memory retrieval. Pre-test administration of nicotine (0.3- and 0.5-mg/kg, s.c.) reversed morphine-induced amnesia. In addition, pre-test intra-CeA injection of MDMA (1-2-µg/rat) with an ineffective dose of nicotine (0.1-mg/kg, s.c.) improved memory retrieval, suggesting the interactive effect of the drugs on memory formation. It should be noted that that pre-test intra-CeA injection of 2-µg/rat of MDMA by itself produced amnesia. Interestingly, pre-test intra-CeA injection of mecamylamine, a nACh receptor antagonist (1-2-µg/rat) or (S)-WAY 100135 (0.25-1-µg/rat), a selective 5-HT1A receptor antagonist inhibited the improvement of morphine-induced amnesia which was produced by pre-test co-injection of nicotine and MDMA. Pre-test intra-CeA injection of the same doses of MDMA, mecamylamine or (S)-WAY 100135 by itself had no effect on morphine-induced amnesia. Moreover, pre-test injection of the same doses of mecamylamine or (S)-WAY 100135 into the CeA alone could not change memory retrieval. Taken together, it can be concluded that there is a functional interaction between morphine, nicotine and MDMA via the CeA nicotinic and serotonergic receptor mechanisms in passive avoidance memory retrieval. Moreover, cross state-dependent memory retrieval may have been induced between the drugs and this probably depends on the rewarding effects of the drugs.
Assuntos
Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/metabolismo , Receptores Nicotínicos/metabolismo , Amnésia/fisiopatologia , Animais , Núcleo Central da Amígdala/fisiopatologia , Relação Dose-Resposta a Droga , Masculino , Mecamilamina/farmacologia , Morfina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Entorpecentes/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Piperazinas/farmacologia , Ratos Wistar , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Serotoninérgicos/farmacologiaRESUMO
The present study examined whether nicotinic acetylcholine receptors (nAChRs) of the CA1 regions of the dorsal hippocampus and medial septum (MS) are involved in cross state-dependent memory retrieval between WIN55, 212-2 (WIN, a non-selective CB1/CB2 receptor agonist) and nicotine or ethanol. Memory retrieval was measured in one-trial step-down type passive avoidance apparatus in male adult mice. Pre-training intraperitoneal administration of WIN (0.1-1mg/kg) dose-dependently impaired memory retrieval when it was tested 24h later. Pre-test systemic administration of nicotine (0.6 and 0.7mg/kg, s.c.) or ethanol (0.5g/kg, i.p.) improved WIN-induced memory impairment, suggesting a cross state-dependent memory retrieval between the drugs. Pre-test intra-CA1 microinjection of nicotine (1 and 2µg/mouse) before systemic administration of an ineffective dose of nicotine (0.5mg/kg, s.c.) or ethanol (0.25g/kg) significantly reversed WIN-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (1 and 3µg/mouse) inhibited cross state-dependent memory between WIN and nicotine or ethanol. Moreover, pre-test intra-MS microinjection of nicotine (1 and 2µg/mouse) in combination with systemic administration of a lower dose of nicotine (0.5mg/kg), but not ethanol (0.25g/kg), improved memory impairment induced by pre-training administration of WIN. On the other hand, in the animals that received pre-training WIN and pre-test systemic administration of nicotine (0.7mg/kg), but not ethanol (0.5g/kg), pre-test intra-MS microinjection of mecamylamine (1-5µg/mouse) inhibited WIN-nicotine state-dependent memory retrieval. It should be noted that pre-test intra-CA1 or intra-MS microinjection of nicotine or mecamylamine by itself had no effect on memory retrieval and also could not reverse memory impairment induced by pre-training administration of WIN. It can be concluded that WIN and nicotine or WIN and ethanol can induce state-dependent memory retrieval. In addition, our results showed that a cross-state dependency between these drugs may be mediated through a cholinergic nicotinic mechanism.
Assuntos
Benzoxazinas/administração & dosagem , Etanol/administração & dosagem , Hipocampo/fisiologia , Memória/fisiologia , Morfolinas/administração & dosagem , Naftalenos/administração & dosagem , Nicotina/administração & dosagem , Receptores Nicotínicos/fisiologia , Septo do Cérebro/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Microinjeções/métodos , Septo do Cérebro/efeitos dos fármacosRESUMO
In this study, we investigated effects of intra-central amygdala (intra-CeA) administrations of a cannabinoid agonist, WIN55,212-2 by itself and its interaction with ß1-adrenoceptor agents on memory consolidation. We used a step-through inhibitory avoidance (IA) task to assess memory in male Wistar rats. The results showed that post-training intra-CeA administrations of different doses of WIN55,212-2 at doses of 0.1 and 0.25 µg/rat impaired memory consolidation (or induced amnesia) as revealed by a decrease in step-through latency on the test day. Post-training intra-CeA injections of a ß1-adrenoceptor agonist, isoprenaline (0.01, 0.025, 0.05 µg/rat) by itself had no significant effect on memory consolidation, while at all doses prevented the amnesia induced by post-training injections of WIN55,212-2 (0.25 µg/rat). Although, post-training intra-CeA administrations of ß1-adrenoceptor antagonist, atenolol alone at different doses (0.01, 0.025, 0.05 and 0.1 µg/rat) had no significant effect, but its co-administrations at doses of 0.05 and 0.1 µg/rat along with an ineffective dose of WIN55,212-2 (0.05 µg/rat) induced amnesia, and at dose of 0.1 µg/rat along with an effective dose of WIN55,212-2 (0.25 µg/rat) increased amnesia that induced by the later drug. Moreover, the improving effect of isoprenaline (0.025 µg/rat) on amnesia induced by WIN55,212-2 (0.25 µg/rat) was prevented by intra-CeA co-injections of atenolol at doses of 0.01 and 0.025 µg/rat. The present results suggest that a ß1-adrenoeceptor mechanism in the central amygdala (CeA) is involved in amnesia induced by post-training intra-CeA injections of WIN55,212-2.
Assuntos
Amnésia/induzido quimicamente , Tonsila do Cerebelo/fisiologia , Benzoxazinas/farmacologia , Moduladores de Receptores de Canabinoides/farmacologia , Memória/fisiologia , Morfolinas/farmacologia , Naftalenos/farmacologia , Receptor CB1 de Canabinoide/agonistas , Receptores Adrenérgicos beta 1/fisiologia , Amnésia/metabolismo , Amnésia/fisiopatologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The present study intended to investigate the involvement of dopaminergic and glutamatergic systems of the basolateral amygdala in amnesia induced by the stimulation of dorsal hippocampal cannabinoid receptors in male Wistar rats. The animals were stereotaxically implanted with guide cannulas in the CA1 region of the dorsal hippocampus and basolateral amygdala (BLA), trained in a step-through type passive avoidance task, and tested 24 h after training to measure memory retrieval. Post-training intra-CA1 microinjection of the nonselective CB1/CB2 receptor agonist WIN55,212-2 (WIN) (0.1-0.5 µg/rat) dose-dependently induced amnesia. Post-training intra-BLA administration of the D1/D2 dopamine receptor agonist apomorphine (0.3 and 0.5 µg/rat) plus intra-CA1 administration of 0.1 µg/rat of WIN, which alone did not induce amnesia, inhibited memory formation. The inhibitory effect of 0.5 µg/rat of WIN (intra-CA1) on memory formation was significantly decreased by the D1 dopamine receptor antagonist SCH23390 (0.1-0.5 µg/rat, intra-BLA) or the D2 dopamine receptor antagonist sulpiride (0.02-0.5 µg/rat, intra-BLA) given 5 min before post-training intra-CA1 microinjection of WIN. It is important to note that single intra-BLA microinjection of the same doses of apomorphine, SCH23390 or sulpiride had no effect on memory retrieval in passive avoidance task. On the other hand, post-training co-administration of N-methyl-d-aspartate (NMDA; 0.03 and 0.05 µg/rat, intra-BLA) plus an ineffective dose of WIN (0.1 µg/rat, intra-CA1) induced amnesia. Furthermore, the inhibitory effect of 0.5 µg/rat of intra-CA1 microinjection of WIN on memory formation was significantly decreased by pre-treatment with intra-BLA microinjection of the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 0.1 and 0.5 µg/rat, intra-BLA). Intra-BLA microinjection of the same doses of NMDA or d-AP5 by itself did not induce any response on memory retrieval. Taken together, these findings support the existence of a functional interaction between dorsal hippocampal and basolateral amygdaloid neural circuits during processing cannabinoid-induced amnesia.
Assuntos
Amnésia/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/patologia , Dopamina/fisiologia , Ácido Glutâmico/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Receptores de Canabinoides/fisiologia , Amnésia/induzido quimicamente , Amnésia/patologia , Tonsila do Cerebelo/metabolismo , Animais , Agonistas de Receptores de Canabinoides , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Vias Neurais/patologia , Ratos , Ratos WistarRESUMO
The aim of the present study was to investigate the existence of possible functional correlation between GABA-A and dopamine (DA) receptors of the dorsal hippocampus and the ventral tegmental area (VTA) in passive avoidance learning. Two guide cannulas were stereotaxically implanted in the CA1 region of the dorsal hippocampus and the VTA of male Wistar rats. In order to measure memory retrieval, the animals were trained in a step-through type passive avoidance task and tested 24 h after training. Post-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.01-0.02 µg/rat) dose-dependently impaired memory retrieval. Post-training intra-VTA administration of SCH23390 (a dopamine D1 receptor antagonist; 0.1-0.8 µg/rat) or sulpiride (a D2 receptor antagonist; 0.5-1.5 µg/rat) decreased the inhibitory effect of muscimol (0.02 µg/rat, intra-CA1) on memory retrieval. Intra-VTA administration of the same doses of SCH23390, but not sulpiride, decreased the step-through latencies. On the other hand, post-training administration of muscimol (0.02 µg/rat) into the VTA inhibited memory retrieval. The administration of SCH23390 (0.01-0.2 µg/rat) or sulpiride (0.1-1 µg/rat) into the CA1 region, immediately after training, had no effect on memory retrieval. Furthermore, the amnesic effect of intra-VTA administration of muscimol was significantly decreased by intra-CA1 administration of sulpiride (0.5 and 1 µg/rat, intra-CA1), but not SCH23390. The practical conclusion is that the relationship between the hippocampus and the VTA may regulate memory formation in passive avoidance learning. Also, the correlation between the hippocampus and VTA by a dopaminergic system may be involved in mediating muscimol-induced amnesia.
Assuntos
Aprendizagem da Esquiva/fisiologia , Neurônios Dopaminérgicos/fisiologia , Neurônios GABAérgicos/fisiologia , Hipocampo/fisiologia , Área Tegmentar Ventral/fisiologia , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Benzazepinas/uso terapêutico , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Agonistas de Receptores de GABA-A/administração & dosagem , Agonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Rememoração Mental/efeitos dos fármacos , Rememoração Mental/fisiologia , Microinjeções , Muscimol/administração & dosagem , Muscimol/antagonistas & inibidores , Muscimol/farmacologia , Ratos , Ratos Wistar , Sulpirida/administração & dosagem , Sulpirida/farmacologia , Sulpirida/uso terapêutico , Área Tegmentar Ventral/efeitos dos fármacosRESUMO
The purpose of this study was to evaluate whether nicotinic acetylcholine receptors of the dorsal hippocampus and the basolateral amygdala (BLA) can potentiate ethanol response in the conditioned place preference (CPP) paradigm. I.p. administration of different doses of ethanol (0.25-1 g/kg) did not induce CPP. However, the higher dose of the drug (1.5 g/kg i.p.) induced place aversion. Furthermore, microinjection of nicotine (0.5-1 microg/rat) into both CA1 regions (intra-CA1) and the BLA (intra-BLA) did not produce a significant CPP. Interestingly, intra-CA1 or -BLA administration of nicotine plus ethanol (0.5 g/kg) during conditioning phase significantly induced a strong CPP. Microinjection of mecamylamine, the nicotinic acetylcholine receptor antagonist, into the CA1 regions or into the BLA did not alter CPP. However, intra-CA1 or -BLA microinjection of mecamylamine (1-4 microg/rat) reversed the response induced by the microinjection of nicotine (1 microg/rat, intra-CA1 or -BLA) plus ethanol (0.5 g/kg i.p.) in the CPP paradigm. On the other hand, the microinjection of nicotine (0.5-1.5 microg/rat) into the BLA, but not into the CA1 regions before the testing phase potentiated the response of ethanol on the expression of conditioned place preference. Moreover, intra-CA1 administration of nicotine plus ethanol increased the locomotor activity on the test day which was reversed by pretreatment with mecamylamine, while other treatments had no effect on locomotor activity. It can be concluded that the activation of nicotinic acetylcholine receptors of the dorsal hippocampus and the basolateral amygdala can potentiate the ethanol response in the CPP paradigm.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Etanol/farmacologia , Receptores Nicotínicos/fisiologia , Tonsila do Cerebelo/metabolismo , Animais , Região CA1 Hipocampal/metabolismo , Condicionamento Clássico/fisiologia , Masculino , Mecamilamina/farmacologia , Microinjeções , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Ratos , Ratos Wistar , RecompensaRESUMO
The current study was conducted to examine the involvement of muscarinic acetylcholine receptors of the amygdala in morphine-induced state-dependent memory retrieval. Male Wistar rats implanted bilaterally with cannulas in the amygdala were submitted to a step-through type passive avoidance task, and tested 24 h after training to measure step-through latency. Post-training s.c. administration of morphine at the doses of 5 and 7.5 mg/kg impaired the memory on the test day, which was restored when the same doses of morphine were used as a pre-test drug. This phenomenon is well known as morphine-induced state-dependent memory retrieval. Bilateral microinjection of the non-selective muscarinic acetylcholine receptor agonist, pilocarpine (0.25 and 0.5 microg/side), into the amygdala with an ineffective dose of morphine (0.5 mg/kg s.c.) significantly improved the memory retrieval and mimicked the effects of pre-test administration of a higher dose of morphine. It should be noted that in the animals that received saline after training and tested following intra-amygdala administration of pilocarpine (0.125, 0.25 and 0.5 microg/side) and those which received post-training morphine (7.5 mg/kg s.c.) and pre-test intra-amygdala microinjection of the same doses of pilocarpine, no significant change was observed in the step-through latencies. On the other hand, pre-test intra-amygdala microinjection of a selective muscarinic acetylcholine receptor antagonist scopolamine (0.125 and 0.25 microg/side) inhibited morphine-induced state-dependent memory retrieval. In addition, no significant changes were seen in memory retrieval of the animals trained before saline treatment and tested following intra-amygdala microinjection of the same doses of scopolamine (0.0625, 0.125 and 0.25 microg/side). Bilateral microinjection of scopolamine into the amygdala reversed the pilocarpine-induced potentiation of the morphine response. In view of the known actions of the drugs used, the present data point to the involvement of amygdala muscarinic acetylcholine receptors in morphine-induced state-dependent memory retrieval.
Assuntos
Tonsila do Cerebelo/metabolismo , Rememoração Mental/efeitos dos fármacos , Morfina/farmacologia , Entorpecentes/farmacologia , Receptores Muscarínicos/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Aprendizagem por Associação/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Microinjeções , Antagonistas Muscarínicos/farmacologia , Ratos , Ratos Wistar , Receptores Muscarínicos/efeitos dos fármacos , Retenção Psicológica/efeitos dos fármacos , Escopolamina/farmacologiaRESUMO
The aim of the present experiments was to investigate whether repeated intra-hippocampal CA1 (intra-CA1) administration of dopaminergic agents can affect morphine-induced conditioned place preference (CPP). Effects of repeated intra-CA1 injections of dopamine (DA) receptor agonists and antagonists on morphine-induced CPP in rats were investigated using an unbiased 3-day schedule of place conditioning. Animals receiving once-daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner: the maximum response was observed with 3 mg/kg morphine. Three days' intra-CA1 injections of apomorphine (0.25-1 microg/rat) followed by 5 days free of the drug, significantly decreased morphine CPP (1 and 3 mg/kg, s.c.). Moreover, pre-treatment with the highest dose of apomorphine (1 microg/rat) altered the effect of morphine to an aversive response. The morphine (1 and 3 mg/kg) CPP was also significantly decreased in animals that previously received three intra-CA1 injections of SKF 38393 (2-9 microg/rat), quinpirole (1-3 microg/rat) or sulpiride (1-3 microg/rat), and significantly increased in animals that had previously received three intra-CA1 injections of SCH 23390 (0.02 microg/rat). The 3-day pre-treatment with apomorphine, SKF 38393 or quinpirole reduced locomotor activity in the test session, while SCH 23390 and sulpiride did not have any influence on locomotor activity. It is concluded that repeated injections of DA receptor agents in the dorsal hippocampus, followed by 5 days free of the drugs, can affect morphine reward.