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The Journal of Neuroscience, April 7, 2004, 24(14):3554-3562; doi:10.1523/JNEUROSCI.5578-03.2004
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Behavioral/Systems/Cognitive
Cocaine Self-Administration Produces a Progressive Involvement of Limbic, Association, and Sensorimotor Striatal Domains
Linda J. Porrino, David Lyons, Hilary R. Smith, James B. Daunais, andMichael A. Nader Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
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.
Key words: cocaine; dopamine; self-administration; striatum; metabolic mapping; primate
Received Dec 18, 2003; revised February 16, 2004; accepted February 18, 2004.
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