Sensitivity to cocaine conditioned reward depends on sex and age

Abstract

Human and animal laboratory studies show that females and males respond differently to drugs and that drug administration during adolescence leads to different behavioral effects than during adulthood. Adult female rats are more sensitive to the behavioral effects of cocaine than adult males, but it is not known if the same effect of sex exists during adolescence. In the present study, sensitivity to the conditioned reward of cocaine was evaluated using a conditioned place preference (CPP) paradigm where adolescent (PND 34) and adult (PND 66) male and female rats were trained and tested for the development of CPP to multiple doses of cocaine. Female rats developed CPP at lower doses than males, regardless of age. In addition, adolescent male and female rats established a CPP at lower doses of cocaine than adult male and female rats, respectively. Thus, both age and sex altered cocaine conditioned reward with the order of sensitivity being adolescent females > adult females > adolescent males > adult males. These data show that adolescents are more sensitive to the conditioned rewarding properties of cocaine than adults and that females respond to lower doses of cocaine compared to males regardless of age.

The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats

“…Overall, females showed a reduced magnitude of CPP compared to the males (Figure 2) while the range of doses producing CPP was shifted to the left (females more sensitive) as previously reported in adolescents and adults (Zakharova et al 2009b)(Russo et al 2003) (Table 2). Prenatal cocaine also appeared to produce smaller effects on CPP in females compared to males but female offspring of the prenatal 30mg/kg (C30) dams did show CPP at more training doses than control females (Table 2).…”

“…Lastly, the minor effects of prenatal cocaine on cocaine reward in females contrasts with the enhanced responses of adult females to cocaine. Adolescent females are more sensitive to cocaine in the CPP test than males and adult females (show CPP at lower training doses; Zakharova et al 2009b), but prenatal exposures and housing conditions have relatively minor effects on overall CPP in females. These results suggest that there are complex interactions between prenatal drug exposures, housing and the development of reward circuits and that these interactions differ in males and females.…”

Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats

“…Female cocaine users have different abuse patterns as compared with males (Griffin et al 1989), and among adolescents the prevalence of cocaine dependence is higher in females than in males (Kandel et al 1997). Consistent with differences in cocaine abuse between males and females, several preclinical studies have reported significant differences in the effects of cocaine between female and male rats, with the predominant finding being that females are more sensitive than males to cocaine, regardless of age (Craft and Stratmann 1996;Festa et al 2004;Sell et al 2000;Walker et al 2001;Zakharova et al 2009). For example, as compared to male rats, female rats selfadminister more cocaine (Lynch and Carroll 1999), show less toxicity to cocaine (Craft and Stratmann 1996), and exhibit greater cocaine-induced hyperactivity and stereotypic responses (Chin et al 2001;Kalivas and Stewart 1991;Post et al 1981).…”

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice

“…Previous reports have shown that female rats acquire cocaine-induced conditioned place preference (CPP) after lower doses and fewer conditioning sessions compared to male rats, suggesting that females may be more sensitive to the rewarding action of cocaine (Russo et al, 2003). Likewise, adolescent (PND34) and adult (PND 66) female rats were more sensitive and acquire cocaine CPP at lower doses than male rats (Zakharova et al, 2009). In general, females have a greater propensity to self-administer cocaine or to exhibit greater sensitivity to the rewarding action of cocaine in the CPP paradigm.…”