A key feature of substance use disorders is continued drug consumption despite aversive consequences. This has been modeled in the animal laboratory by pairing drug self-administration with electric shock, thereby punishing drug intake (Deroche-Gamonet et al. 2004). In the present experiments, we examined the effects of punishment on i.v. cocaine self-administration by adding histamine to the cocaine solution with three different animal models of high and low vulnerability to drug abuse: rats selectively bred for high (HiS) and low (LoS) saccharin consumption, rats selected for high (HiI) and low (LoI) impulsivity, and sex differences. Animals were allowed to self-administer cocaine (0.4. mg/kg/infusion) to establish a baseline of operant responding. Histamine (4.0. mg/kg/infusion) was then added directly into the cocaine solution and its consequent effects on self-administration were compared to baseline. The histamine. +. cocaine solution was then replaced with a cocaine-only solution, and the rats' operant responding was again compared to baseline. Concurrent histamine exposure was effective in reducing cocaine consumption in all groups of rats; however, LoS and female rats took longer to return to baseline levels of cocaine consumption after histamine was removed compared to HiS and male rats. These data suggest that the reduction of drug self-administration by aversive consequences may differ in groups that vary in drug use vulnerability Such results may inform pharmacological strategies that enhance the negative aspects of drug consumption.
Bibliographical noteFunding Information:
This research was supported by NIDA/NIH grants R01 DA003240 , P20 DA024196 (Project 1), and K05 DA15267 (MEC). We thank Natalie Zlebnik, Amy Saykao, and Seth Johnson for their technical assistance.
- Sex differences