Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Donna J. Toufexis


In the early stages of instrumental learning, behavior is goal-directed and sensitive to changes in the value of the instrumental outcome. As learning progresses, an association forms between the response and stimuli within the learning environment, such that after sufficient repetition, responding is evoked automatically in the presence of these stimuli and is insensitive to changes in outcome value. The reflexive nature of these types of behaviors has led to their classification as instrumental habits. The emergence of habitual behavior is thought to involve parallel processes that are mediated by distinct neural substrates. Regions of the prefrontal cortex, amygdala, and dorsal striatum have been heavily implicated in these processes. We have previously found that female rats develop habitual behaviors within a distinct range of training that is markedly less than what has been shown to support habitual responding in males, suggesting a sex difference in the rate of habit formation.

In Chapters 1 and 2, we review the background literature and describe the general methods used to investigate the sex difference in habit formation. In Chapter 3, we investigate the role of central dopamine neurotransmission, a major modulator of dorsal striatal function, in rapid habit formation in female rats. We conducted a series of experiments in which female and male rats were administered methamphetamine with the aim of sensitizing central dopamine prior to instrumental training. Following training, we tested for sensitivity to lithium chloride reinforcer devaluation. In females, Vehicle groups responded in a habitual manner following training at both ends of the transition range, while Meth groups remained goal-directed at both training levels. Conversely, male rats demonstrated goal-directed behavior at these training levels regardless of drugpretreatment condition. However, when given more extended training, male rats in the Meth group responded habitually, whereas Vehicles were goal-directed. Together, these results suggest that dopamine sensitization effects habit formation in a sexually dimorphic manner, and baseline sex differences in dorsal striatal dopamine may play a key role in the sex difference in habit formation.

In Chapter 4, we aimed to determine the role of ovarian hormones during instrumental acquisition on rapid habit formation in female rats. Ovariectomized female rats were given subcutaneous silastic capsules that release low diestrus levels of 17-b estradiol. Rats were assigned to one of three hormone treatment conditions: no additional hormone replacement (Low E2 group), replacement with proestrus levels of E2 (High E2 group), or replacement with E2 followed by progesterone (E2+P group). Hormone replacement occurred twice during acquisition to mimic hormone fluctuations during the natural estrous cycle. All subjects received the lowest amount of training at which we have reliably observed habitual behavior in intact female rats. At test, the Low E2 and High E2 groups demonstrated responding that was sensitive to devaluation, indicating goal-directed behavior. In contrast, the E2+P group exhibited a pattern of habitual responding which suggested the suppression of goal-directed processes. These data indicate that the rapid habit formation observed in intact female rats is not facilitated in low ovarian hormone states, nor in the presence of cycling proestrus estrogen. Indeed, cycling proestrus estrogen together with progesterone appears to be necessary during acquisition to establish habit, possibly by acting at cortical regions involved in suppressing goal-directed processes.



Number of Pages

122 p.