Examining the Roles of Sex, Methamphetamine, and Degree of Training in Habit Formation in Rats

Addiction is characterized by a progressive loss of executive control over drug-seeking and consumption, and may be associated with a behavioral shift from instrumental goal-directed actions to stimulus-response habits. Sex differences in drug addiction have been linked to changing hormone levels across the estrous cycle, and females exhibit a particular vulnerability to psychostimulants such as cocaine and amphetamines. Psychostimulants and estrogen both influence dopaminergic activity in the dorsal striatum, a region of the brain in which dopamine activity is thought to mediate the shift from action to habit. In the present set of experiments, we examined the roles of sex, amphetamine, and degree of training on habit formation in rats. To test habit formation in each experiment, animals were trained on a variable interval (VI) schedule of reinforcement to nose-poke for sucrose pellet reinforcers, then the sucrose was devalued in half of the animals by pairing its presentation with injections of lithium chloride (LiCl) to induce nausea. Animals for whom the sucrose was paired with LiCl acquired a conditioned taste aversion for the sucrose reinforcer. When tested in extinction, paired animals who remained goal-directed should inhibit their responding for the devalued sucrose, whereas animals in habit should be insensitive to the devaluation and respond at a similar rate as their non-devalued counterparts. Experiment 1 examined the role of sex in habit formation in which intact male and female rats received identical training, devaluation, and testing in two separate within-sex experiments. After 240 reinforcer exposures females exhibited habitual behavior whereas males remained goal-directed. In Experiment 2, female rats were ovariectomized (OVX) and half were given cyclic estrogen replacement. All animals received either pre-exposure to methamphetamine (METH) or vehicle. Following exposure to 120 reinforcers, a level of training that had previously been shown to be subthreshold to habit formation in males, all female groups demonstrated goal-directed responding at test, revealing a lack of effect of hormone replacement or drug pre-treatment on habit formation in OVX females at this level of reinforcer exposure. Experiment 3 aimed to determine the degree of nose-poke training that would be sub-threshold to habit formation in intact females, and two groups were given different amounts of training. Both groups exhibited habitual responding, indicating that habit threshold in females is lower than hypothesized. Overall, these experiments suggest that females shift into habitual behavior earlier in training than males, and further experiments need to be conducted to determine how factors such as hormone milieu and psychostimulant exposure influence this progression