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Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling.

ABSTRACT: Poor decision making and elevated risk taking, particularly during adolescence, have been strongly linked to drug use; however the causal relationships among these factors are not well understood. To address these relationships, a rat model (the Risky Decision-making Task; RDT) was used to determine whether individual differences in risk taking during adolescence predict later propensity for cocaine self-administration and/or whether cocaine self-administration causes alterations in risk taking. In addition, the RDT was used to determine how risk taking is modulated by dopamine signaling, particularly in the striatum. Results from these experiments indicated that greater risk taking during adolescence predicted greater intake of cocaine during acquisition of self-administration in adulthood, and that adult cocaine self-administration in turn caused elevated risk taking that was present following 6 weeks of abstinence. Greater adolescent risk taking was associated with lower striatal D2 receptor mRNA expression, and pharmacological activation of D2/3 receptors in the ventral, but not dorsal, striatum induced a decrease in risk taking. These findings indicate that the relationship between elevated risk taking and cocaine self-administration is bi-directional, and that low striatal D2 receptor expression may represent a predisposing factor for both maladaptive decision making and cocaine use. Furthermore, these findings suggest that striatal D2 receptors represent a therapeutic target for attenuating maladaptive decision making when choices include risk of adverse consequences.

SUBMITTER: Mitchell MR

PROVIDER: S-EPMC3924529 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling.

Mitchell Marci R MR Weiss Virginia G VG Beas B Sofia BS Morgan Drake D Bizon Jennifer L JL Setlow Barry B

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20131022 4

Poor decision making and elevated risk taking, particularly during adolescence, have been strongly linked to drug use; however the causal relationships among these factors are not well understood. To address these relationships, a rat model (the Risky Decision-making Task; RDT) was used to determine whether individual differences in risk taking during adolescence predict later propensity for cocaine self-administration and/or whether cocaine self-administration causes alterations in risk taking. ...[more]

PMID: 24145852

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Project description:Circadian rhythm disturbances have long been associated with the development of psychiatric disorders, including mood and substance use disorders. Adolescence is a particularly vulnerable time for the onset of psychiatric disorders and for circadian rhythm and sleep disruptions. Preclinical studies have found that circadian rhythm disruption (CRD) impacts the brain and behavior, but this research is largely focused on adult disruptions. Here, we sought to determine the long-term behavioral and neurobiological effects of CRD during early adolescence by exposing mice to 12 h shifts in the light/dark cycle. We hypothesized that adolescent CRD would have a greater effect on psychiatric-related behaviors, relative to adult disruption. To identify possible mechanisms, we also measured gene expression in brain regions relevant to circadian rhythms, mood and reward. We found that disruption during early adolescence, but not adulthood, persistently increased exploratory drive (risk-taking behavior) and cocaine preference when tested later in life. Interestingly, we found sex differences when intravenous cocaine self-administration was tested. While female mice with a history of adolescent CRD had a greater propensity to self-administer cocaine, as well as increased motivation and cue-induced reinstatement, male adolescent CRD mice had reduced motivation and extinction responding. Overall, adolescent CRD in mice caused persistent increases in risky behavior, cocaine reward and cocaine self-administration, which suggests that CRD during adolescence may predispose individuals towards substance use disorders. Importantly, we found that many transcripts were affected by adolescent CRD and these were largely distinct across sex and brain region. Future research is required to elucidate how adolescent CRD affects behaviors relevant to mood- and substance use-related disorders across the 24-hour day, as well as to identify intervention strategies to alleviate disruption during adolescence and novel therapeutic approaches once symptoms have begun.

Dataset Information

Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling.

Publications

Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling.

Similar Datasets

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