A COMMON MECHANISM MEDIATES LONG-TERM CHANGES IN SYNAPTIC TRANSMISSION AFTER CHRONIC COCAINE AND MORPHINE

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