Mar 18, 2019

Selective D2 and D3 receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Daniel F ManvichDavid Weinshenker

Abstract

The dopamine D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for the treatment of several diseases including schizophrenia, Parkinson's disease, and substance use disorders. However, studies investigating the D3R's precise role in dopamine neurotransmission or how it may be exploited to modulate responses to drugs of abuse have produced contrasting results, in part because most D3R-targeted compounds often also interact with D2 receptors (D2R). To resolve this issue, we set out to systematically characterize and compare the consequences of selective D2R or D3R antagonists on the behavioral-stimulant properties of cocaine in mice, and to identify putative neurobiological mechanisms underlying their behavior-modifying effects. Pretreatment with the selective D2R antagonist L-741,626 attenuated, while pretreatment with the selective D3R antagonist PG01037 enhanced, the locomotor-activating effects of both acute cocaine administration as well as sensitization following repeated cocaine dosing. While both antagonists potentiated cocaine-induced increases in presynaptic dopamine release, we report for the first time that D3R blockade uniquely facilitated dopamine-mediated excitation of D1-expressing medium spi...Continue Reading

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Mentioned in this Paper

Study
Presynaptic Terminals
Drug Use Disorders
Schizophrenia
Adenosine receptor antagonist
Synaptic Transmission
Molecular_function
Response to Cocaine
Administration Procedure
Locomotion

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