Chunk #22 — 1. Definitions and conceptual framework for compulsivity in addiction — 1.3. Animal models of compulsivity in addiction as defined by increased drug taking: Escalation in drug self-administration with prolonged access
The hypothesis that compulsive cocaine use is accompanied by a chronic perturbation in brain reward homeostasis has been tested in an animal model of escalation in drug intake with prolonged access combined with measures of brain stimulation reward thresholds. Animals implanted with intravenous catheters and allowed differential access to intravenous self-administration of cocaine showed increases in cocaine self-administration from day to day in the long-access group (6 h; LgA) but not in the short-access group (1 h; ShA). The differential exposure to cocaine self-administration had dramatic effects on reward thresholds that progressively increased in LgA rats but not in ShA or control rats across successive self-administration sessions (Ahmed et al., 2002). Elevation in baseline reward thresholds temporally preceded and was highly correlated with escalation in cocaine intake (Figure 5). Post-session elevations in reward thresholds failed to return to baseline levels before the onset of each subsequent self-administration session, thereby deviating more and more from control levels. The progressive elevation in reward thresholds was associated with the dramatic escalation in cocaine consumption that was observed previously. After escalation had occurred, an
