Subchronic cocaine treatment enhances cocaine-induced dopamine efflux, studied by in vivo intracerebral dialysis

Repeated administration of cocaine in animals results in behavioral sensitization. In order to investigate the neurochemical mechanism underlying such behavioral sensitization, we designed the following two experiments. In both experiments, rats were pretreated with cocaine (20 mg/kg i.p.) or saline, once daily for 14 consecutive days. Exp. 1: 7 days after withdrawal from the drug, the stereotyped behavioral response to a challenge of cocaine (20 mg/kg i.p.) was measured. Exp. 2: 7 days after withdrawal from the drug, we measured extracellular dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) after the challenge administration of cocaine using an in vivo intracerebral dialysis technique. The rats pretreated with cocaine (20 mg/kg i.p.) exhibited behavioral augmentation in response to a challenge of cocaine. The challenge administration of cocaine caused an increase in DA and a decrease in DOPAC. The DA level in the striatal perfusates of the cocaine-pretreated rats was significantly greater than that in the saline-pretreated rats. These results suggest that the increased extracellular DA concentration in the striatum plays an important role in the cocaine-induced behavioral sensitization.