Olanzapine Attenuates the Morphine-Induced Conditioned Place Preference: The Involvement of the D2-Like Dopamine Receptors.

OBJECTIVE

Opioid use disorder is associated with persistent molecular and cellular changes in the brain, leading to compulsive drug-seeking behaviors. This study aimed to evaluate the effects of olanzapine (OLZ), a D2-like dopamine receptor (D2R) antagonist, on morphine dependence using the conditioned place preference (CPP) model.

METHODS

Morphine-induced CPP was established by subcutaneous (sc) administration of morphine (5 mg/kg) for three consecutive days. OLZ at doses of 1.5, 3, and 4.5 mg/kg was administered intraperitoneally (ip) during different phases of CPP: acquisition, expression, and extinction. Behavioral assessments included measurement of conditioning scores and locomotor activity. D2R protein expression in the hippocampus (HIP) was evaluated using western blotting.

RESULTS

OLZ reduced both acquisition and expression of morphine-induced CPP in a dose-dependent manner. Additionally, OLZ facilitated extinction by shortening the duration of the extinction phase. Western blot analysis showed a significant reduction in D2R protein expression in the expression and extinction phases in the OLZ-treated groups compared to the morphine-only group. Importantly, effective doses of OLZ did not impair locomotor activity.

CONCLUSION

OLZ attenuates morphine-induced CPP and downregulates D2R expression in the HIP without affecting general locomotor function. These findings suggest a potential therapeutic role for OLZ in the management of opioid-related behaviors. Further research is needed to determine its clinical relevance.