Dopamine sensitization by methamphetamine treatment prior to instrumental training delays the transition into habit in female rats

Abstract

Early in instrumental learning, behavior is goal-directed and sensitive to changes in the value of the instrumental outcome. With sufficient repetition, responding becomes insensitive to changes in outcome value, or habitual. We have previously found that females transition into habit over a distinct range of training from 120 to 160 reinforced responses. This low level of instrumental training is markedly less than what has been shown to support habitual responding in male rats. To begin to investigate the early development of habit in females, we conducted a series of experiments in which we pretreated female rats with methamphetamine (METH) with the aim of sensitizing central dopamine, a major modulator of striatal function, prior to instrumental nose-poke training at the beginning and at the endpoint of the transition range in females. Following training, we tested for sensitivity to reinforcer devaluation (RD), which was conducted by repeatedly pairing reinforcers previously earned during training with lithium chloride (LiCl)-induced illness. As a counterpoint, a series of similar experiments was conducted separately in male rats. Additionally, in order to ascertain the validity of using nose-poke as an instrumental response, we compared sensitivity to devaluation between the Pavlovian approach towards the food magazine and the nose-poke response.In females, Vehicle groups responded in a habitual manner at both training levels (120 and 160 reinforced responses), whereas METH groups remained sensitive to devaluation. This suggests that increasing central dopamine delays habit formation in female rats. In male rats, Vehicle groups demonstrated goal-directed responding following training with 120 and 320 reinforced responses, and marginally goal-directed responding,with 160. METH-pretreated males were sensitive to devaluation at the 120 and 160 training levels, however, following more extended training to 320 reinforced responses, METH-pretreated males responded in a habitual manner, indicating that increasing central dopamine can advance habit formation in male rats. Overall, these results suggest that METH pretreatment maintains goal-directed responding in female rats when they are typically transitioning to habitual control of instrumental behavior and can advance habit formation in male rats given sufficient instrumental training. In addition, we found differential RD sensitivity of the nose-poke response used during instrumental training compared to Pavlovian approach towards the food magazine, confirming that there is a distinction between these two behaviors and that nose-poking is a valid instrumental response.