Domperidone Modulates Hippocampal D2 Expression, Facilitates Extinction, and Attenuates Morphine-Induced Conditioned...

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Peripheral dopamine D2 receptors (D2R) are involved in reward processing.
• The specific role of peripheral D2R in morphine-induced reward, particularly conditioned place preference (CPP), is not well understood.

Purpose of the Study:

• To investigate the effect of peripheral D2R blockade using domperidone (DOM) on morphine-induced CPP in rats.
• To assess DOM's influence on D2R expression in the hippocampus.

Main Methods:

• Male Wistar rats received morphine (5 mg/kg, SC) to establish CPP.
• Domperidone (0.5, 1, 2 mg/kg) was administered during acquisition, expression, or extinction phases.
• Behavioral CPP was measured, and hippocampal D2R levels were analyzed using Western blot.

Main Results:

• Domperidone significantly attenuated morphine-induced CPP during acquisition and expression phases, with the 1 mg/kg dose being most effective.
• The 1 mg/kg dose of domperidone facilitated extinction and prevented reinstatement of CPP.
• Domperidone treatment decreased hippocampal D2R expression during the expression and extinction phases.

Conclusions:

• Peripheral D2R antagonism by domperidone modulates morphine-induced CPP and hippocampal D2R expression.
• Peripheral dopaminergic mechanisms are implicated in opioid reward.
• Domperidone's peripheral action shows potential therapeutic value for opioid use disorders.