5-HT2A Serotonin Receptor Density in Adult Male Rats’ Hippocampus after Morphine-based Conditioned Place Preference

Introduction: A close interaction exists between the brain opioid and serotonin (5-HT)&nbsp;neurotransmitter systems. Brain neurotransmitter 5-HT plays an important role in the regulation&nbsp;of reward-related processing. However, a few studies have investigated the potential role of&nbsp;5-HT2A receptors in this behavior. Therefore, the aim of the present study was to assess the influence of morphine and Conditioned Place Preference (CPP) on the density of 5-HT2A receptor&nbsp;in neurons of rat hippocampal formation. Methods: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days&nbsp;(intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a&nbsp;hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days&nbsp;1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections,&nbsp;their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1&nbsp;gene expression was examined with a semi-quantitative RT-PCR method. Results: Our data showed that the maximum response was obtained with 2.5 mg/kg of morphine.&nbsp;The density of 5-HT2A receptor in different areas of the hippocampus increased significantly at&nbsp;sham-morphine and CPP groups (P<0.05). On the other hand, the CPP groups had more 5-HT2A&nbsp;receptors than sham-morphine groups and also the sham-morphine groups had more 5-HT2A&nbsp;receptors than the control groups. Conclusion: We concluded that the phenomenon of conditioned place preference induced by&nbsp;morphine can cause a significant increase in the number of serotonin 5-HT2A receptors in neurons&nbsp;of all areas of hippocampus.