Cocaine Self-Administration Produces a Progressive Involvement of Limbic, Association, and Sensorimotor Striatal Domains

TLDR

The primate striatum comprises limbic, cognitive, and sensorimotor domains, and while cocaine effects are classically linked to the ventral (limbic) region, recent rodent studies suggest dorsal (cognitive and sensorimotor) involvement. The study aimed to map the spatial pattern of cocaine‑induced functional changes across the entire striatum in monkeys self‑administering cocaine and to determine how chronic exposure alters this pattern. Rhesus monkeys received 0.3 mg/kg cocaine injections for either 5 days (n = 4) or 100 days (n = 4) under a fixed‑ratio schedule, with 30 reinforcers per session, and metabolic activity was measured at the end of the 5th or 100th session, compared to food‑reinforced controls (n = 6). Early cocaine exposure reduced ventral striatal activity and only modestly affected dorsal regions, whereas chronic exposure amplified and extended these effects dorsally to encompass most of the caudate and putamen, indicating a progressive shift from limbic to sensorimotor and cognitive striatal domains.

Abstract

The primate striatum is composed of limbic, cognitive, and sensorimotor functional domains. Although the effects of cocaine have generally been associated with the ventral striatum, or limbic domain, recent evidence in rodents suggests the involvement of the dorsal striatum (cognitive and sensorimotor domains) in cocaine self-administration. The goals of the present studies were to map the topography of the functional response to cocaine throughout the entire extent of the striatum of monkeys self-administering cocaine and determine whether this response is modified by chronic exposure to cocaine. Rhesus monkeys were trained to self-administer 0.3 mg/kg per injection cocaine for 5 d (initial stages; n = 4) or 100 d (chronic stages; n = 4) and compared with monkeys trained to respond under an identical schedule of food reinforcement ( n = 6). Monkeys received 30 reinforcers per session, and metabolic mapping was conducted at the end of the 5th or 100th self-administration session. In the initial phases of cocaine exposure, self-administration significantly decreased functional activity in the ventral striatum, but only in very restricted portions of the dorsal striatum. With chronic cocaine self-administration, however, the effects of cocaine intensified and spread dorsally to include most aspects of both caudate and putamen. Early experiences with cocaine, then, involve mainly the limbic domain, an area that mediates motivational and affective functions. In contrast, as exposure to cocaine continues, the impact of cocaine impinges progressively on the processing of sensorimotor and cognitive information, as well as the affective and motivational information processed in the ventral striatum.