Research into the neural bases of cocaine abuse has established an essential role of the mesolimbic dopamine (DA) system innervating the nucleus accumbens (NAc). Recently, the nigrostriatal DA system innervating the dorsolateral striatum (DLS), a region necessary for acquiring habits, has been implicated in cocaine abuse. According to this view, drug self- administration gradually recruits striatal circuitry beyond the ventromedial striatum (accumbens), eventually spreading to the DLS. Rats will self-administer cocaine in a tone discrimination task, 6 hours/day, 7 days a week for 4 weeks to model both the long access/escalation pattern of intake described by Ahmed and Koob (1998) and the accompanying changes in striatum that have been shown to occur in the chronically drug-exposed brain by Porrino et al. (2004). Among numerous single unit recording studies during cocaine self-administration in well trained subjects, none have ever i) recorded DLS neurons, ii) recorded NAc shell, core and DLS simultaneously, or iii) tracked their phasic firing patterns from the first session throughout an extended period of cocaine self-administration. All three are the focus of the proposed studies. The instrumental response will be a vertical head movement or licking a dry spout, in order to target DLS neurons related specifically to one of those two movements. Single unit activity will be recorded simultaneously from NAc medial shell and core neurons, from non-sensorimotor DLS neurons and from DLS neurons related specifically to vertical head movement or to licking. Single neurons will be tracked across sessions to assess changes within and between subregions. The spatial and temporal resolution of the proposed single unit recordings would bring an unprecedented level of detail to the tracking of long-term neural changes associated with chronic cocaine abuse, and assure the acquisition of new and valuable information that will be necessary ultimately for mechanistic explanations.
Chronic cocaine self-administration causes changes in circuitry of the human basal ganglia. Rats will self-administer cocaine in a long access/escalation pattern to model these reported changes. Single neuron impulse activity will be tracked across self-administration sessions to assess changes in rat basal ganglia circuits. The spatial and temporal resolution of single unit recordings would provide valuable information relevant to mechanistic explanations of long-term neural changes associated with chronic cocaine abuse.
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