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

PACCHIONI AM,; GABRIELE A; SEE RE

Rosario, Santa Fe, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2009

Sociedad Argentina de Farmacologia Experimental

Accumulating evidence has suggested that increased drugseekingin cocaine addiction may occur as progressive druginducedrecruitment of more dorsal areas of the striatum exertgreater control over drug-seeking via habitual stimulus-responsemediated behaviors. The current study evaluated thecontribution of the dorsal striatum (dlCPu) to cocaine-seekingfollowing varied histories of cocaine self-administration anddifferent periods of abstinence. We predicted that cocaineseekingafter longer cocaine histories would come under greatercontrol of the dlCPu. Following implantation of a jugularcatheter and bilateral intracranial guide cannulae, male Sprague-Dawley rats were trained to press a lever to receive cocaineinfusions and were then divided into two groups: 1-hr and 6-hraccess for 15 days. We then examined relapse of cocaineseekingafter 1, 14, and 60 days of abstinence. Before eachrelapse test, subjects received bilateral infusion of vehicle, or acombination of baclofen/muscimol into the dlCPu. All animalsshowed robust responding during each of the relapse tests aftervehicle infusion, regardless of prior cocaine self-administrationhistory. Inactivation of the dlCPu significantly attenuatedresponding on the relapse test days, with proportionally greaterdecrements seen in animals with the longest duration of cocaineself-administration. These data support the possibility that thedlCPu controls drug-seeking to a larger degree at the time ofrelapse in individuals with a history of greater cocaine use.