The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively bred High-Responder and Low-Responder rats

Abstract

Individual differences in exploratory behavior can predictably influence psychostimulant selfadministration behavior. Male rats that exhibit a high degree of locomotor activity in a novel environment (High Responders, HR) will self-administer cocaine more readily than males exhibiting low levels of novelty-induced locomotion (Low Responders, LR). The present experiment investigates the combined influences of the sex of an individual and individual phenotypes in noveltyinduced locomotion to predispose animals to acquire cocaine self-administration behavior, in male and female rats selectively bred for the HR-LR phenotypes. We first established that HR females, like their male counterparts, exhibit a dramatically greater locomotor response to novelty and less anxiety-like behavior than do LR females. While locomotor behavior was subtly influenced by estrous stage, with both HR and LR females showing increased activity during metestrus and diestrus compared to proestrus and estrus, the effect did not obscure HR-LR differences. When male and female HR-LR animals were trained to self-administer cocaine (2 h/day, 5 days/wk × 3 wk, 0.2 mg cocaine/kg/infusion), HR males and females acquired cocaine self-administration significantly faster than their LR counterparts. Furthermore, HR females self-administered significantly more cocaine than all other groups. In conclusion, female rats, like males, exhibit HR-LR phenotypes that predict rapidity of acquiring cocaine self-administration. Moreover, HR females self-administer more cocaine than HR males and both LR groups.

Initial nicotine sensitivity in humans as a function of impulsivity

“…Higher scores on measures related to novelty seeking and response disinhibition (factor 2) tended to be associated with greater nicotine reward in men but less reward or no difference in women. Recent animal research similarly suggests that individual differences in novelty seeking may influence drug reinforcement differentially as a function of sex (e.g., Davis et al 2008). Our findings could help explain prior research showing greater nicotine reward and reinforcement in men compared to women (Perkins et al , 2002a).…”

Novel Cues Reinstate Cocaine-Seeking Behavior and Induce Fos Protein Expression as Effectively as Conditioned Cues

“…The rewarding properties of novelty have been documented in humans and animals (Bardo et al, 1989(Bardo et al, , 1996Besheer et al, 1999), and motivation for novelty predicts individual sensitivity to drug reward and reinforcement (Belin et al, 2011;Davis et al, 2008;Nadal et al, 2002;Pelloux et al, 2006;Piazza et al, 1989Piazza et al, , 2000Suto et al, 2001). We therefore suggest that the novel stimuli may have activated similar reinforcement and motivation processes as those involved in conditioned reinforcement-seeking behavior.…”

Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

“…Relative to bLRs, bHRs are more impulsive (19), more aggressive (20), and more likely to signtrack to food-and drug-associated cues (19). Although we have previously shown that these selectively bred rats also differ in their initial propensity to take cocaine (24), the present study assesses individual differences in cocaine addiction liability by exposing bHR and bLR rats to a prolonged self-administration procedure ( Fig. 1), and subsequently assessing some of the diagnostic criteria for addiction (25), including the persistence of drug-seeking behavior and, following abstinence, the propensity for drug-primed and cue-induced reinstatement, using a rat relapse model (for review, see ref.…”