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 selfadministration 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. Neuropsychopharmacology (2014) 39, 955-962;

Cocaine use is associated with high levels of impulsive choice (greater discounting of delayed rewards) in humans, but the cause/effect relationships between cocaine use and impulsive choice are not fully understood. In previous work, we found that both experimenter- and self-administration of fixed quantities of cocaine caused lasting increases in impulsive choice in rats. The present study extended these findings by taking into account baseline impulsive choice prior to self-administration, and by allowing rats free access to cocaine. Male Long-Evans rats were trained in a delay discounting task in which they made discrete-trial choices between small immediate and large delayed food rewards. Half of the rats were then implanted with intravenous catheters and, following recovery, allowed to self-administer cocaine HCl (1.0 mg/kg/infusion) in 6 hour sessions over 14 days. Control rats orally self-administered a sucrose solution under similar conditions. Upon completion of self-administration training, rats remained abstinent for 3 weeks before retesting in the delay discounting task. Cocaine and control groups did not differ prior to self-administration, but afterward, the cocaine group showed greater impulsive choice (fewer choices of large, delayed rewards) than controls. Additional analyses revealed that the effects of cocaine on impulsive choice were intake-dependent; rats classified as “low intake” did not differ from controls, whereas rats classified as “high intake” were significantly more impulsive than both controls and their pre-cocaine baseline. These findings are consistent with the idea that cocaine-induced, pharmacologically based neural adaptations promote the development of impulsive decision making.

Interaction with social peers may increase rates of drug self-administration, but a recent study from our laboratory showed that social interaction may serve as a type of alternative reward that competes with drug taking in adolescent male rats. Based on those previous results, the current study examined sex differences in preference for social interaction compared to amphetamine (AMPH) in adolescent rats using the conditioned place preference (CPP) paradigm. Similar to previous results with males, females showed AMPH CPP regardless whether they were individual- or pair-housed. In contrast to males, however, females failed to show social CPP, and they did not prefer a peer-associated compartment over an AMPH-associated compartment in a free-choice test. In separate experiments, dopamine (DA) and serotonin (5-HT) metabolite levels were measured in adolescent males and females that were exposed acutely to peer interaction, no peer interaction, AMPH, or saline. In amygdala, levels of the DA metabolite dihydroxyphenylacetic acid (DOPAC) were altered more in response to peer interaction in males than females; in contrast, there was a greater amygdala DOPAC response to AMPH in females. Furthermore, there were greater changes in the 5-HT metabolite 5-HIAA in females than in males following social interaction. These results indicate that the ability of peer interactions to reduce drug reward is greater in adolescent males than females, perhaps due to a greater ability of social cues to activate limbic reward mechanisms in males or a greater ability of AMPH cues to activate limbic reward mechanisms in females.

No abstract

No abstract