Oct 9, 2018

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

BioRxiv : the Preprint Server for Biology
Daniel F ManvichDavid Weinshenker


Background: The D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for the treatment of several diseases including schizophrenia, Parkinsons disease, and substance use disorders. However, studies investigating the modulatory impact of D3R antagonism on dopamine neurotransmission or the effects drugs of abuse have produced mixed results, in part because D3R-targeted compounds often also interact with D2 receptors (D2R). The purpose of this study was to compare the consequences of selective D2R or D3R antagonism on the behavioral effects of cocaine in mice, and to identify the neurobiological mechanisms underlying their modulatory effects. Methods: We characterized the effects of selective D2R or D3R antagonism in mice on 1) basal and cocaine-induced locomotor activity, 2) presynaptic dopamine release and clearance in the nucleus accumbens using ex vivo fast scan cyclic voltammetry, and 3) dopamine-mediated signaling in D1-expressing and D2-expressing medium spiny neurons using ex vivo electrophysiology. Results: Pretreatment with the selective D2R antagonist L-741,626 attenuated, while pretreatment with the selective D3R antagonist PG01037 enhanced, the locomotor-activating effects of acute and repeated coca...Continue Reading

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Mentioned in this Paper

In Vivo
Presynaptic Terminals
Central Nervous System Stimulant [EPC]
Cyclic Peptides
Drug Use Disorders
Central Nervous System Stimulants
Antagonist Muscle Action

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