23 Thus, these effects were documented to be mediated exclusively by the kappa-opioid receptor. In different studies, we further explored the

impact of extended-access (10 hours) versus short-access (3 hours) and also highversus low-dose cocaine impact on self-administration, cocaine-induced reinstatement, and on brain mRNA levels.25 It was again found that the escalation of cocaine self-administration under long-access conditions was greater than under short-access, and was dose-dependent. Further, we showed that such longaccess, with animals who were allowed self-administration Inhibitors,research,lifescience,medical for 10 hours at high doses, resulted in an Inhibitors,research,lifescience,medical increased susceptibility to drug-induced relapse.25 There were also GW9662 clinical trial differences in neurobiological indices, specifically levels of gene expression in those animals who were allowed to have long access and high doses, compared with short access. There were significant increases in proenkephalin gene expression in the caudate-putamen following longaccess and high-dose self-administration.25

Further, it was found that dopamine D2 receptor mRNA levels in the caudate-putamen and nucleus accumbens were significantly correlated with cocaine reinstatement.25 Inhibitors,research,lifescience,medical However, there was no significant correlation between neuropeptide mRNA levels and cocaine-induced reinstatement.25 Body weight progressively declined in the long-access self-administering rats.25 In parallel to these findings, food consumption was also significantly reduced Inhibitors,research,lifescience,medical in each group during self-administration, but the reduction in food intake was much greater in the long-access rats.25 During the 10-day extinction period, food consumption was significantly greater in the long-access, high-dose rats compared with both the short-access and the low-dose rats, and, in fact, food consumption during

extinction in the high-dose group was significantly greater than pre-self-administration Inhibitors,research,lifescience,medical baseline levels.25 These findings are similar to observations made by our group in human cocaine addicts in a controlled research setting. They have negative implications for some groups of people, where the desire for thinness, or the desire for attaining the self-image of thinness, may contribute to continued cocaine (or other stimulant) self-administration. PAK6 The many findings from these long-access, high-dose cocaine self-administration rodent studies, both our more recent ones, as well as our earlier ones, along with the studies from other groups, particularly those of Koob and of Miczek, suggest that the findings may not only be relevant potentially for the human situation, but provide new insights for further study both in laboratory-based and human research paradigms.