Brain and behavior · 2026
Olanzapine Attenuates the Morphine-Induced Conditioned Place Preference: The Involvement of the D2-Like Dopamine Receptors.
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Firozjaei Farkhondeh Rzazzaghi-, Pour Amineh Sadat Zahiri-, Ghavipanjeh Gholamreza, Ghaderi Amir, Haghparast Abbas, Ardjmand Abolfazl, Banafshe Hamid Reza
Аннотация
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.
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.