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Updated: Mar 15, 2026

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
5-HT2A Serotonin Receptor Density in Adult Male Rats' Hippocampus after Morphine-based Conditioned Place Preference
Rabie Mohammadi1, Mehrdad Jahanshahi1, Seyed Behnamedin Jameie2
1Department of Anatomy, Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Introduction:
A close interaction exists between the brain opioid and serotonin (5-HT) neurotransmitter systems. Brain neurotransmitter 5-HT plays an important role in the regulation of reward-related processing. However, a few studies have investigated the potential role of 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 in neurons of rat hippocampal formation.
Methods:
Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 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. The density of 5-HT2A receptor in different areas of the hippocampus increased significantly at sham-morphine and CPP groups (P<0.05). On the other hand, the CPP groups had more 5-HT2A receptors than sham-morphine groups and also the sham-morphine groups had more 5-HT2A receptors than the control groups.
Conclusion:
We concluded that the phenomenon of conditioned place preference induced by morphine can cause a significant increase in the number of serotonin 5-HT2A receptors in neurons of all areas of hippocampus.
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