Apr 8, 2020

Effects of Selective Dopamine D2 or D3 Receptor Antagonism on Morphine-Induced Locomotion in Mice

BioRxiv : the Preprint Server for Biology
C. A. Botz-ZappDaniel F Manvich

Abstract

Rationale: The dopamine D3 receptor (D3R) has garnered interest as a pharmacotherapeutic target for the treatment of opioid use disorder (OUD). Recent evidence suggests that D2R and D3R antagonism oppositely affect the locomotor-activating effects of cocaine, but whether this pattern extends to opioid-induced hyperactivity remains unresolved. Objective: This study compared the impact of selective D2R vs. D3R antagonists on the locomotor-activating effects of acute and repeated morphine administration in mice. Catalepsy following D2R vs. D3R antagonism alone or in combination with morphine was also assessed. Methods: C57Bl/6J mice were pretreated with either the highly-selective D3R antagonist PG01037 (vehicle, 10.0 mg/kg) or the selective D2R antagonist L-741,626 (vehicle, 10.0 mg/kg) and tested for 1) locomotor activity induced by acute morphine administration (10.0 - 56.0 mg/kg), 2) locomotor sensitization following repeated morphine administration (56.0 mg/kg), or 3) catalepsy after administration of either antagonist alone or in combination with morphine (10.0 - 56.0 mg/kg). Results: In locomotion studies, both PG01037 and L-741,626 shifted the acute morphine dose-response function rightward/downward, although the inhibitor...Continue Reading

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Size
Derivatives
Cell Division
ACE2
ACE2
Yeasts
Adverse Effects
Etiology
Adaptation
Apoptosis

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