Higher locomotor response to cocaine in female (vs. male) rats selectively bred for high (HiS) and low (LoS) saccharin intake

Abstract

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 cocaineinduced locomotor activity and the development of locomotor sensitization, which was determined by comparing the effects of cocaine injection 1 with injection 6, which was 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 injections 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 only 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.

Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats

“…Prior to activity testing, rats received 4 days of ALLO or vehicle pretreatment at 8:30 A.M. Locomotor activity was then assessed in daily 45-min sessions beginning at 9:00 A.M. for 5 days, while rats also continued to receive ALLO or vehicle daily. To measure locomotor activity, a circular track (inner diameter 46 cm; outer diameter 71 cm; height 25 cm) previously described by Carroll et al (2007) was used.…”

The role of impulsive behavior in drug abuse

“…HiS rats escalated their drug intake to higher levels and showed greater reinstatement of cocaine-seeking behavior than LoS rats (Perry et al 2006). In addition, HiS females showed greater dysregulation of cocaine intake than LoS females (Carroll et al 2007b) and higher rates of cocaine-induced locomotor activity (Carroll et al 2007a). HiS males and females were also more impulsive on a DD task rewarded with food (Perry et al 2007) and a go/no-go task rewarded by i.v.…”

Sex differences in animal models of psychiatric disorders

“…In the conditioned place aversion, when amphetamine at low doses is used as the aversive stimulus, female rats acquire stronger aversions than males and extinguish it more slowly (Roma et al, 2008). Lastly, in studies examining sex differences in locomotor sensitization, female rats are more sensitive than male rats to drug-induced locomotor sensitization (Festa and Quinones-Jenab, 2004a;Festa et al, 2004b;Nazarian et al, 2004;Carroll et al, 2007).…”

“…In the conditioned place aversion, when amphetamine at low doses is used as the aversive stimulus, female rats acquire stronger aversions than males and extinguish it more slowly (Roma et al, 2008). Lastly, in studies examining sex differences in locomotor sensitization, female rats are more sensitive than male rats to drug-induced locomotor sensitization (Festa and Quinones-Jenab, 2004a;Festa et al, 2004b;Nazarian et al, 2004;Carroll et al, 2007).In summary, addiction is perhaps one of the fields in behavioural pharmacology that has advanced substantially in studying sex differences and several excellent reviews provide a more in-depth view of such progress (Lynch, 2006;Becker and Hu, 2008;Fattore et al, 2008; Carroll and Anker, 2010). …”