Early environmental enrichment and impoverishment differentially affect addiction-related behavioral traits, cocaine-taking, and dopamine D_2/3 receptor signaling in a rat model of vulnerability to drug abuse.

ABSTRACT:

Rationale

Risk factors for drug addiction include genetics, environment, and behavioral traits such as impulsivity and novelty preference (NP), which have been related to deficits in striatal dopamine (DA) D_2/3-receptors (D_2/3R) and heightened amphetamine (AMPH)-induced DA release. However, the influence of the early rearing environment on these behavioral and neurochemical variables is not clear.

Objectives

We investigated the influence of early rearing environment on striatal D_2/3R availabilities and AMPH-induced DA release in relation to impulsivity, NP, and propensity to drug self-administration (SA) in "addiction-prone" Roman high- (RHA) and "addiction-resistant" Roman low-avoidance (RLA) rats.

Methods

Animals were reared post-weaning in either environmental enrichment (EE) or impoverishment (EI) and were assessed at adulthood for impulsivity, NP, and propensity to cocaine SA. EE and EI rats were also scanned using single-photon emission computed tomography to concurrently measure in vivo striatal D_2/3R availability and AMPH-induced DA release.

Results

EE vs. EI was associated with heightened impulsivity and a lack of NP in both rat lines. Higher dorsal striatal D_2/3R densities were found in RHA EE and higher AMPH-induced DA release in RLA EE. Both impulsivity and NP were negatively correlated to dorsal striatal D_2/3R availabilities and positively correlated with AMPH-induced DA release in EI but not in EE. EE vs. EI was related to a faster rate of cocaine intake and elevated active timeout responses in RHAs.

Conclusion

Our results suggest non-monotonic, environment-dependent, relationships between impulsivity, NP, and D_2/3R-mediated signaling, and suggest that EI vs. EE may decrease the reinforcing effects of psychostimulants in predisposed individuals.

SUBMITTER: Belles L 

PROVIDER: S-EPMC8629910 | biostudies-literature |

REPOSITORIES: biostudies-literature