Co-administration of either a selective D1 or D2 dopamine antagonist with methamphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis.

Repeated administration of amphetamine or methamphetamine (MAP) causes behavioral sensitization in animals. Recently, several studies have revealed that in vivo release of dopamine from presynaptic nerve terminals of mesotelencephalic dopamine neurons is enhanced when sensitized animals are rechallenged with a psychostimulant. The present study investigated the effect of co-administration of SCH 23390 (a selective D1 dopamine receptor antagonist) or YM-09151-2 (a selective D2 dopamine receptor antagonist) prior to each MAP injection for 14 days on dopamine efflux in the striatal perfusates using in vivo dialysis. After 3 months drug abstinence, MAP challenge alone produced augmented stereotypy in the MAP group, but not in the control, the SCH 23390 + MAP or the YM-09151-2 + MAP group. In parallel with this behavioral observation, the degree to which dopamine efflux increased following the MAP challenge was significantly greater in the MAP group than that in the control, SCH 23390 + MAP group and the YM-09151-2 + MAP groups. While dopamine efflux after MAP challenge did not differ between the control and the YM-09151-2 + MAP group, it was greater in the SCH 23390 + MAP group than the control group. These results indicate that both D1 and D2 dopamine receptors play a role in the formation of behavioral sensitization, but with different mechanisms.