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- W2897511619 abstract "Abstract Background The D 3 receptor (D 3 R) 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 modulatory impact of D 3 R antagonism on dopamine neurotransmission or the effects drugs of abuse have produced mixed results, in part because D 3 R-targeted compounds often also interact with D 2 receptors (D 2 R). The purpose of this study was to compare the consequences of selective D 2 R or D 3 R 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 D 2 R or D 3 R 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 D 1 -expressing and D 2 -expressing medium spiny neurons using ex vivo electrophysiology. Results Pretreatment with the selective D 2 R antagonist L-741,626 attenuated, while pretreatment with the selective D 3 R antagonist PG01037 enhanced, the locomotor-activating effects of acute and repeated cocaine administration. While both antagonists potentiated cocaine-induced increases in presynaptic DA release, D 3 R blockade uniquely facilitated DA-mediated excitation of D 1 -expressing medium spiny neurons in the nucleus accumbens. Conclusions Selective D 3 R antagonism potentiates the behavioral-stimulant effects of cocaine in mice, an effect that is in direct opposition to that produced by selective D 2 R antagonism or nonselective D 2 -like receptor antagonists, likely by facilitating D 1 -mediated excitation in the nucleus accumbens. These findings provide important insights into the neuropharmacological actions of D 3 R antagonists on mesolimbic dopamine neurotransmission." @default.
- W2897511619 created "2018-10-26" @default.
- W2897511619 creator A5016547032 @default.
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- W2897511619 creator A5075263192 @default.
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- W2897511619 creator A5090310054 @default.
- W2897511619 date "2018-10-09" @default.
- W2897511619 modified "2023-09-27" @default.
- W2897511619 title "Selective D2 and D3 receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens" @default.
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- W2897511619 doi "https://doi.org/10.1101/439398" @default.