5-HT1B receptor agonist CP 94,253 reduces cocaine intake in female rats post-abstinence and after resuming self-administration

Approximately five million Americans suffer from cocaine use disorder with no FDA approved pharmaceutical to help their path to recovery (Yerby, 2019). Serotonin is heavily implicated in cocaine use and in the reward system, and is therefore a suggested target for pharmaceuticals aiming to aid in psychostimulant addiction (Sarlin, 2019; Clark and Neumaier, 2001). CP 94,253, a 5-HT1BR agonist, has been shown to increase cocaine intake during maintenance of daily cocaine self-administration, though it has also been shown to decrease intake after a period of forced abstinence (Parsons et al., 1998; Pentowski et al., 2009). While a decrease in cocaine intake post-abstinence is promising post-abstinence, it remains to be seen whether this is a viable option if patients relapse. Most experiments are conducted with male rats, though an increasing amount of data has come to light on the differing effects of drugs on male and female rats (Mennenga and Bimonte-Nelson, 2014). Previous studies conducted through our lab have shown no difference in cocaine self-administration behavior across the estrous cycle phases with CP 94,253. It remains to be seen however, whether CP 94,253 would function dissimilarly in female rats than in male rats. This experiment studied the effects of CP 94,253 on post-abstinence and post-resumption cocaine self-administration in free-cycling female rats across two doses of cocaine. It was shown that CP 94,253 reduces cocaine intake both post-abstinence and post-resumption, suggesting that this pharmacotherapy would work in cases of relapse, and that there are no sex differences in its effects. While more studies should be conducted with locomotion and stress tests, thus far this experiment provides further evidence for the validity of CP 94,253 to be a promising pharmacotherapeutic option for future investigation.