دانلود رایگان مقاله تعامل بین سیستم های سروتونین و کانابینوئید هیپوکامپ

ABSTRACT

Functional interaction between cannabinoid and serotonin neuronal systems have been reported in different tasks related to memory assessment. The present study investigated the effect of serotonin 5-HT4 agents into the dorsal hippocampus (the CA1 region) on spatial and object novelty detection deficits induced by activation of cannabinoid CB1 receptors (CB1Rs) using arachidonylcyclopropylamide (ACPA) in a non-associative behavioral task designed to forecast the ability of rodents to encode spatial and nonspatial relationships between distinct stimuli. Post-training, intra-CA1 microinjection of 5-HT4 receptor agonist RS67333 or 5-HT4 receptor antagonist RS23597 both at the dose of 0.016 g/mouse impaired spatial memory, while cannabinoid CB1R antagonist AM251 (0.1 g/mouse) facilitated object novelty memory. Also, post-training, intraperitoneal administration of CB1R agonist ACPA (0.005-0.05 mg/kg) impaired both memories. However, a subthreshold dose of RS67333 restored ACPA response on both memories. Moreover, a subthreshold dose of RS23597 potentiated ACPA (0.01 mg/kg) and reversed ACPA (0.05 mg/kg) responses on spatial memory, while it potentiated ACPA response at the dose of 0.005 or 0.05 mg/kg on object novelty memory. Furthermore, effective dose of AM251 restored ACPA response at the higher dose. AM251 blocked response induced by combination of RS67333 or RS23597 and the higher dose of ACPA on both memories. Our results highlight that hippocampal 5-HT4 receptors differently affect cannabinoid signaling in spatial and object novelty memories. The inactivation of CB1 receptors blocks the effect of 5-HT4 agents into the CA1 region on memory deficits induced by activation of CB1Rs via ACPA.

4. Discussion

The main goal of the present work was to investigate the potential role of the hippocampal 5-HT4 receptors in spatial and object novelty detection memory deficits induced by activation of CB1 receptors via ACPA. This study examined interaction between 5- HT4 and cannabinoid CB1 systems in consolidation of memories assessed in a non-associative learning task.Our findings with post-training, intraperitoneal administration of cannabinoid CB1 receptor agonist ACPA are consistent with previous findings showing that ACPA impaired both spatial and object novelty detection memory consolidations in the same line of mice [31]. In addition, our data indicate that microinjection of cannabinoid CB1 antagonist AM251 into the CA1 region of hippocampus facilitated object novelty memory consolidation. Also, effective dose of AM251 prevented both ACPA-induced memory impairments. Regarding to these results and the crucial role of hippocampus in memory formation, we can suggest that ACPA via activation of CB1 receptors in the hippocampus impairs memory consolidation.