Dorsal striatum mediation of cocaine-seeking after varied periods of cocaine self-administration and withdrawal in rats

SEE RE; GABRIELE A; PACCHIONI AM

Chicago, IL, USA

Congreso; 39th Annual Meeting of Neurosciences; 2009

Society for Neuroscience

Accumulating evidence has suggested that increased drug-seeking in cocaine addiction may occur as progressive drug-induced recruitment of more dorsal areas of the striatum exert greater control over drug-seeking via habitual stimulus-response mediated behaviors. The dorsolateral caudate/putamen (dlCPu) has been implicated in habit learning and data from our laboratory has shown that reversible inactivation of the dlCPu prior to reinstatement testing in a rat model of relapse significantly attenuated cocaine-seeking. However, no studies of drug-seeking at the time of relapse have established the time course of withdrawal emergent patterns, or the effects of variations in prior drug intake that may impact the transition to greater dorsal striatum control. Therefore, the current study evaluated the contribution of the dlCPu to cocaine-seeking following varied histories of cocaine self-administration and different periods of abstinence. We predicted that cocaine-seeking after longer cocaine histories would come under greater control of the dlCPu, such that animals with limited cocaine exposure would be less affected by dlCPu inactivation than animals with more prolonged drug experience. Following implantation of a jugular catheter and bilateral intracranial guide cannulae, male Sprague-Dawley rats were trained to press a lever along a FR-1 schedule of reinforcement for cocaine infusions (0.2 mg/50 ul). Initial cocaine self-administration consisted of 5-6 days of 2-hr daily sessions. Subjects were then divided into three groups: 2-hr access (5 days of 2-hr sessions), 1-hr access (15 days of 1-hr sessions), and 6-hr access (15 days of 6-hr sessions). We then examined relapse of cocaine-seeking in the self-administration chamber after 1, 14, and 60 days of abstinence. During relapse tests, lever responding was recorded, but had no programmed consequences. In between the test days, animals remained in their home cages. For each relapse test, subjects received bilateral infusion of vehicle, or a combination of a GABA-B and GABA-A agonist mixture (baclofen/muscimol, 1.0/0.1 mM) into the dlCPu prior to a 2-hr test session. All animals showed robust responding during each of the relapse tests after vehicle infusion, regardless of prior cocaine self-administration history. Inactivation of the dlCPu significantly attenuated responding on the relapse test days, with proportionally greater decrements seen in animals with the longest duration of cocaine self-administration. These data support the possibility that the dlCPu controls drug-seeking to a larger degree at the time of relapse in individuals with a history of greater cocaine use.