Role of dopamine D1- and D2-like receptor mechanisms in drug-seeking following methamphetamine self-administration in rats

It has been suggested that dopaminergic mechanisms mediate relapse to drug-seeking behavior and both D1- and D2-like receptor mechanisms have been implicated. In contrast to self-administration of other drugs, there is a relative paucity of studies that has examined the pharmacological basis of methamphetamine (MA) seeking. Accordingly, the present study used an animal model of drug-seeking to determine the role of D1- and D2-like receptor mechanisms in relapse to MA abuse. Rats were trained to self-administer MA, and then responding was extinguished by replacing the MA solution with vehicle. Experimenter-administered injections of MA or the dopamine uptake inhibitor, GBR 12909, reinstated extinguished responding in a dose-dependent manner. The D1-like antagonist, SCH 23390 attenuated drug-seeking but the D2-like antagonist, eticlopride, was ineffective. The results suggest that MA-seeking is predominantly mediated by DA D1-like receptor mechanisms. These findings are in contrast to the literature on drug-seeking following self-administration of other drugs, and suggest that relapse to different drugs of abuse may rely upon different DA receptor mechanisms.