LOCOMOTOR SENSITIZATION AND DECREASE IN [H-3] MAZINDOL BINDING TO THEDOPAMINE TRANSPORTER IN THE NUCLEUS-ACCUMBENS ARE DELAYED AFTER CHRONIC TREATMENTS BY GBR12783 OR COCAINE

Rats were treated once daily for 15 consecutive days with either cocai ne or the specific dopamine uptake inhibitor methoxy)ethyl]-4-(3-pheny l-2-(propenyl)-piperazine (GBR12783) at a dose (10 mg/kg) that given a cutely increases locomotor activity. Two or 14 days after the last adm inistration, the motor stimulant responses of rats to a challenge dose (5 mg/kg) of the drug administered previously were compared with the motor stimulant responses of rats daily injected with solvent. A sensi tization to the acute stimulant locomotor effect of these drugs was on ly observed 14 days after cessation of chronic treatments, After this withdrawal period, autoradiographic analysis revealed a significant de crease in the desipramine-insensitive [H-3]mazindol binding to the dop amine transporter in the shell of the nucleus accumbens. Na change was noticed in other regions with high dopamine content: core of nucleus accumbens, striatum, olfactory tubercle, substantia nigra and ventral tegmental area. Absence of concomitant decrease in [H-3]dihydrotetrabe nazine labeling, which indicates lack of effect on vesicular monoamine transporters, suggests that the decrease in accumbal [H-3]mazindol bi nding did not result from a cytotoxic effect on corresponding dopamine neurons. in addition, 14 days after the last administration of GBR127 83, the levels of dopamine and metabolites (dihydroxyphenylacetic acid , homovanillic acid) and the ability of acute GBR12783 to synergize wi th haloperidol-induced increases in these metabolites were not modifie d either in the whole nucleus accumbens or in the striatum.