Rats selectively bred for high saccharin consumption (HiS) self-administer more oral ethanol and i.v. cocaine than those selectively bred for low saccharin consumption (LoS). Male and female drug-seeking-prone (HiS) and -resistant (LoS) rats were used in the present experiment to test the prediction that cocaine-induced locomotor activity and sensitization varied with sex and their selective breeding status (HiS and LoS). All rats were intermittently exposed over 2 weeks to pairs of sequential saline and cocaine injections, separated by 45 min. The first 5 pairs of injections, each separated by 2-3 days (10-12 days total), were given to examine the development of cocaine-induced locomotor activity and the development of locomotor sensitization, which was determined by comparing the effects of cocaine injection 1 with injection 6 (given 2 weeks after the 5 pairs of intermittent injections). Results indicated that after the first injection pair (saline, cocaine) the HiS and LoS groups did not differ (saline vs. cocaine) in locomotor activity; however, after cocaine injection pairs 1, 5, and 6, HiS females were more active than HiS males and LoS females. There were also significant phenotype differences (HiS > LoS) in locomotor activity after cocaine injections 5 and 6. There was a weak sensitization effect in cocaine-induced locomotor activity in HiS females after cocaine injection 5 (compared to 1); however it was not present after injection 6 or in other groups. The lack of a strong sensitization effect under these temporal and dose conditions was inconsistent with previous reports. However, the results showing HiS > LoS and females > males on cocaine-induced activity measures are consistent with several measures of cocaine-seeking behavior (acquisition, maintenance, escalation, extinction, and reinstatement), and they suggest that cocaine-induced locomotor activity and sensitization are behavioral markers of drug-seeking phenotypes.
Bibliographical noteFunding Information:
The authors wish to thank Drs. Erin Larson, Jennifer Newman, and Jennifer Perry for their editorial assistance and review of the manuscript and Justin Anker for his technical assistance and editorial comments. This work was supported by NIH/NIDA grants T32 DA007097-25 (ADM), R01 DA003240-23 (MEC) and K05 DA015267-06 (MEC).
- Locomotor activity
- Saccharin intake
- Sex differences