The mesolimbic system is known to play a role in self-administration of opioids and psychostimulants. Although morphine and cocaine act by separate cellular mechanisms initially, the present study describes a common change in synaptic regulation of dopamine cells in the ventral tegmental area 1 week after termination of chronic treatment with either drug. Normally, D1 receptor activation augmented the amplitude of a gamma-aminobutyric acid type B (GABA(B)) inhibitory postsynaptic potential (IPSP), but in drug-experienced animals, D1 receptor activation caused an inhibition of the GABA(B) IPSP. The inhibition was blocked by adenosine A1 receptor antagonists and by agents that disrupted the metabolism of cAMP. This long-lasting dopamine-adenosine interaction may be one mechanism involved in dopamine-mediated craving and relapse to drug-seeking behaviors.