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There are multiple neurotransmitters and neuromodulator systems mediating memory formation among which the endocannabinoid system plays a critical role in the memory formation by modulating the release of many neurotransmitters. Nucleus accumbens appears to have a site in the central of neuronal circuits of the limbic system and to be responsible for the integration and consolidation of inputs from other parts of the brain. In this study the influence of bilateral intra-nucleus accumbens shell microinjections of cannabinoid receptor agents on memory consolidation in adult male rats using passive avoidance task was investigated. The results showed that the intra-accumbens shell microinjection of ACPA as a CB1 receptor agonist (6 ng/rat) immediately after training decreased passive avoidance memory consolidation, while administration of its antagonist (AM251) at different doses did not affect passive avoidance memory consolidation. However, co-administration of AM251 (60 ng/rat) with an effective dose of ACPA prevented the impairment memory consolidation induced by ACPA. These results suggest that the accumbens shell cannabinoid system as a modulating system is involved in aversive memory consolidation including passive avoidance memory.

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Basolateral Amygdala is an important site of anxiety. Interactions between α-adrenergic and opioidergic systems in Basolateral amygdale were used for investigation anxiety and memory. The elevated plus-maze has been employed. The male wistar rats were used for this test. The site of BLA was cannulated bilaterally. Rats we injected morphine (4, 5.6 mg/kg) intraperitonealy, while clonidine (1, 2, 4 µg/rat) and yohimbin (0.5, 1,2 µg/rat) were injected to BLA. Open arm time percentage (%OAT), open arm entry (%0AE) and locomotor activity were determined by this behavioral test. Retention tested 24 hours later. Administration of morphine (6mg/kg) increased the OAT% in anxiety test, indicating anxiolytic-like effect. Intra Basolateral amygdala infusion of clonidine (4μg/rat) has an anxiolytic-like effect. While co-administration clonidine (4μg/rat) and in effective dose of morphine (4mg/kg) showed significant increase of OAT% in anxiety test; thus presenting anxiolytic response. Intra Basolateral amygdala administration of yohimbine (2μg/rat) decreased OAT% indicating of decrease anxiety-like behavior. While co-administration of intra Basolateral amygdala clonidine (4μg/rat) and effective dose of morphine (6mg/kg) showed a significant increase of OAT%, presenting anxiolytic response; co-administration of ineffective doses of morphine (4mg/kg) and yohimbine (1μg/rat) with the effective dose of clonidine (4μg/rat) showed that yohimbine could reverse the anxiolytic-like effect of morphine and clonidine. It should be noted that there are no significant changes in locomotor activity. The results indicate that morphine creates the compromise changes in adrenergic neurons of Basolateral amygdala by changing the α-adrenergic system on anxiety.                                                                                                                                                                  

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Septohippocampal system plays an important role in regulating fear and anxiety behaviors. In this study, the effects of histamine injected into the dorsal hippocampus and opioidergic agents into medial septum on the anxiety-like behaviors in rats were analyzed, using the Elevated Plus-Maze (EPM) test. Injection of 1 and 5 μg/rat histamine into dorsal hippocampus had no effect on anxiety-like behavior, while injection of 10 μg/rat histamine increased the percentage of open arm time (%OAT) and open arm entry (%OAE), which indicated the anxiolytic effects of histamine. Microinjection of morphine, μ-opioid receptor agonist, into the medial septum (1μg/rat) increased the (%OAT) and (%OAE). Doses of 0.25, 0.5 μg/rat morphine had no effect on anxiety. Co-administration of histamine ineffective dose (1μg/rat) to the dorsal hippocampus and ineffective dose of morphine (0.25µg/rat) to the medial septum increased the (%OAT) and (%OAE). Subsequently, injection of different doses of naloxone (1, 2, 4 µg/rat), as an opioid receptor antagonist, into the medial septum in the presence and absence of an effective dose of histamine (10 µg/rat) in the dorsal hippocampus, was studied. Injection of naloxone (4 µg/rat) into medial septum decreased the (%OAT) and (%OAE), but did not alter the locomotor activity, which indicated the anxiogenic effects of naloxone. Simultaneous injection of histamine (10 µg/rat) into dorsal hippocampus with doses of naloxone (1, 2, 4 µg/rat) into the medial septum, indicate anxiolytic effects and increased %OAT and %OAE in Elevated Plus Maze, although when the dose of naloxone was 4μg/rat, this effect was less observed. The results indicate that hippocampus histaminergic system interact with medial septum opioidergic system and the interaction of these systems modulates anxiety behavior.