Decreased cell proliferation in the dentate gyrus of rats after repeated administration of cocaine.

Cell proliferation in the dentate gyrus of hippocampus was assessed using in vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats that were administered cocaine (20 mg/kg) for 14 consecutive days. Rats showed increased stereotypy at a challenge dose of cocaine after 1 week of withdrawal, suggesting the acquisition of behavioral sensitization. Twenty-four hours after final injection of repetitive cocaine administration, a 26% decrease in BrdU-positive cells was observed, compared with control rats. However, this returned to control level within 1 week. No differences were observed in rats that received a single injection of cocaine. Differentiation of newly formed cells was not influenced. These data imply that the regulation of hippocampal cell proliferation by cocaine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization.