In a series of studies, dopamine partial agonists have not only been shown to reverse psychostimulant withdrawal but also to block the increase in psychostimulant self-administration associated with extended access. Dopamine partial agonists decrease the reinforcing effects of psychostimulant drugs in nondependent limited access paradigms (Izzo et al., 2001; Pulvirenti et al., 1998). However, animals with extended access show an increased sensitivity to a dopamine partial agonist (Wee et al., 2007). Long-access rats administered a dopamine D2 partial agonist showed a shift to the left of the dose-response function similar to results observed with dopamine antagonists (Ahmed and Koob, 2004). These results, combined with the observation that dopamine partial agonists also can reverse psychostimulant withdrawal, suggest that dysregulation of dopamine tone may contribute to the motivational effects of drug withdrawal.
