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Scientific article
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English

Repeated cocaine intake differentially impacts striatal D2/3 receptor availability, psychostimulant-induced dopamine release, and trait behavioral markers of drug abuse

Published inInternational journal of molecular sciences, vol. 24, no. 17, no. Role of Dopamine in Health and Disease: Biological Aspect 2.0, 13238
Publication date2023-08-26
First online date2023-08-26
Abstract

Current research indicates that altered dopamine (DA) transmission in the striatum contributes to impulsivity and novelty-seeking, and it may mediate a link concerning a higher susceptibility to drug abuse. Whether increased susceptibility to drug abuse results from a hyperdopaminergic or hypodopaminergic state is still debated. Here, we simultaneously tracked changes in DA D2/3 receptor (D2/3R) availability and amphetamine-(AMPH)-induced DA release in relation to impulsivity and novelty-seeking prior to, and following, cocaine self-administration (SA) in Roman high- (RHA) and low- (RLA) avoidance rats. We found that high-impulsive/high novelty-seeking RHA rats exhibited lower D2/3R availabilities and higher AMPH-induced DA release in the striatum that predicted higher levels of cocaine intake compared with RLAs. Cocaine SA did not alter striatal D2/3R availability or impulsivity in RHA or RLA rats. Critically, cocaine exposure led to a baseline-dependent blunting of stimulated DA release in high-impulsive/high novelty-seeking RHA rats only, and to a baseline-dependent increase in novelty-seeking in low-impulsive/low novelty-seeking RLA rats only. Altogether, we propose that susceptibility to drug abuse results from an innate hyper-responsive DA system, promoting impulsive action and novelty-seeking, and producing stronger initial drug-reinforcing effects that contribute to the initiation and perpetuation of drug use. However, with repeated cocaine use, a tolerance to drug-induced striatal DA elevations develops, leading to a compensatory increase in drug consumption to overcome the reduced reward effects.

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Citation (ISO format)
URUENA MENDEZ, Ginna Paola et al. Repeated cocaine intake differentially impacts striatal D2/3 receptor availability, psychostimulant-induced dopamine release, and trait behavioral markers of drug abuse. In: International journal of molecular sciences, 2023, vol. 24, n° 17, p. 13238. doi: 10.3390/ijms241713238
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ISSN of the journal1422-0067
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