Habitual alcohol seeking: time course and the contribution of subregions of the dorsal striatum

Abstract

Background: Addictions are defined by a loss of flexible control over behavior. The development of response habits might reflect early changes in behavioral control. The following experiments examined the flexibility of alcohol-seeking after different durations of self-administration training and tested the role of the dorsal striatum in the control of flexible and habitual alcohol self-administration.

Methods: Rats were trained to lever-press to earn unsweetened ethanol (EtOH) (10%). The sensitivity of the lever-press response to devaluation was assessed by prefeeding the rats either EtOH or sucrose before an extinction test after different amounts of training (1, 2, 4, and 8 weeks). We subsequently tested the role of the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) in controlling alcohol seeking with reversible inactivation techniques (baclofen/muscimol: 1.0/.1 mmol/L, .3 μL/side).

Results: We find that operant responding for EtOH early in training is goal-directed and reduced by devaluation, but after 8 weeks of daily operant training, control has shifted to a habit-based system no longer sensitive to devaluation. Furthermore, after relatively limited training, when responding is sensitive to devaluation, inactivation of the DMS greatly attenuates the alcohol-seeking response, whereas inactivation of the DLS is without effect. In contrast, responding that is insensitive to devaluation after 8 weeks of training becomes sensitive to devaluation after inactivation of the DLS but is unaffected by inactivation of the DMS.

Conclusions: These experiments demonstrate that extended alcohol self-administration produces habit-like responding and that response control shifts from the DMS to the DLS across the course of training.

Figure 1. Time course for the development of habitual alcohol seeking

Mean lever presses (+/− SEM) in 10-min following either pre-feeding of alcohol (devalued) or sucrose (non-devalued) after different amounts of training. Responding was significantly reduced by devaluation after (A) 1 week or (B) 2 weeks of self-administration, but not after (C) 4 weeks or (D) 8 weeks of training, suggests that 8 weeks of daily training is sufficient for the development of an alcohol “habit” in rats. N=17, ** indicates p<.01; * indicates p<.05. Separate groups of rats were trained and tested only once following either two (E) or eight (F) weeks of training. Again, rats decreased responding following devaluation of the alcohol outcome following two weeks but not eight weeks of training. N=10–11 per group.

Figure 2. Sensitivity of responding for sucrose reward to devaluation following either two or eight weeks of training

Mean lever presses (+/− SEM) in 10-min following pre-feeding of either sucrose (devalued) or polycose (non-devalued). Responding for sucrose was sensitive to devaluation at both the two week (A) and eight week (B) time points suggesting that responding for sucrose does not transition to habitual performance within this time frame. However, rats given home cage access to ethanol (C) over the course of instrumental training did not show sensitivity to devaluation indicating that non-contingent ethanol promoted habit formation. N=9–13 per group. * indicates p<.05.

Figure 3. Effects of inactivation of the DMS or DLS on sensitivity to devaluation following either two or eight weeks of training

Mean lever presses (+/− SEM) in 10- min following devaluation or control treatment and infusion of saline or muscimol into either the DMS or DLS. (A&B) A significant effect of devaluation was observed following two weeks of training for rats in both the DMS and DLS groups following saline infusion. (A) This sensitivity was lost following inactivation of the DMS. (B) Sensitivity to devaluation was unaffected by inactivation of the DLS. (C&D) Following 8 weeks of training, performance of rats in both the DMS and DLS groups was not sensitive to devaluation of the alcohol outcome. (C) Rats in the DMS group remained insensitive to devaluation following inactivation. (D) Inactivation of the DLS lead to a renewed sensitivity to devaluation. N= 11 or 12 per group. * indicates p<.05.

Figure 4. Schematic representation of cannulae placements within the DMS or DLS for rats in Experiment 2

The location of the injector tips is represented by squares for the DMS group and circles for the DLS group. Numbers on the left indicate the distance anterior to bregma. Coronal images after (48).