Effect of Testosterone on Maintenance of Morphine-Induced Conditioned Place Preference: Androgen and M-Opioid Receptor Gene Expressions in Pfc and Nac of Rats Publisher



Charkhgard N ; Torkamanboutorabi A ; Zahmatkesh M ; Vousooghi N ; Farahmandfar M ; Moghadam NN
Source: Clinical Psychopharmacology and Neuroscience Published:2026

Abstract

Objective: Rewarding properties of androgens have been suggested. This research aimed to assess the effect of androgen system during the extinction period on morphine induced conditioned place preference (CPP). Androgen and m-opioid receptor (m-OR) gene expression were also evaluated in prefrontal cortex (PFC) and nucleus accumbens (NAc) in the male rats. Methods: CPP was induced by morphine injection (3, 5 and 7 mg/kg, s.c.) for three consecutive days. Testosterone (androgen receptor [AR] agonist, 2.5 mg/kg; i.m.) or flutamide (AR antagonist 10 mg/kg, i.m.) were administered in subsequent extinction period. In two castration groups, one group was considered as control and the other one received testosterone during extinction phase. The mRNA expression levels of m-OR and ARs in PFC and NAc were evaluated using quantitative real-time PCR following CPP reinstatement. Results: Testosterone prolonged while flutamide shortened extinction period. Castration facilitated morphine-extinction and testosterone could not reverse this effect. The expression of m-OR and ARs were increased in PFC and NAc of castrated animals compared to control group which were reversed by testosterone. This effect was not reversed by testosterone for m-OR in PFC. Conclusion: Our data indicated that decreased level of testosterone facilitates extinction period in morphine CPP model in male rats. This result could be due to the changes in the expression of opioid and androgenic receptors in PFC and NAc. This study confirms the crucial role of androgen system in modulating drug reward. © 2026, Korean College of Neuropsychopharmacology.