ASCENDING AFFERENT REGULATION OF RAT MIDBRAIN DOPAMINE NEURONS

Standard, extracellular single-unit recording techniques were used to examine the electrophysiological and pharmacological responsiveness of midbrain dopamine (DA) neurons to selected, ascending afferent inputs . Sciatic nerve stimulation-induced inhibition of nigrostriatal DA (NS DA) neurons was blocked by both PCPA (5-HT synthesis inhibitor) and 5, 7-DHT (5-HT neurotoxin), suggesting mediation by a serotonergic (5-HT) system. Direct stimulation of the dorsal raphe (which utilizes 5-HT a s a neurotransmitter and inhibits slowly firing NSDA neurons) inhibite d all mesoaccumbens DA (MADA) neurons tested. Paradoxically, DPAT, a 5 -HT1A agonist which inhibits 5-HT cell firing, enhanced sciatic nerve stimulation-induced inhibition of NSDA neurons. MADA neurons were not inhibited by sciatic nerve stimulation and, therefore, could not be te sted in this paradigm. In contrast to the dorsal raphe, electrical sti mulation of the pedunculopontine tegmental nucleus preferentially exci ted slowly firing NSDA and MADA neurons. Thus, both excitatory and inh ibitory ascending afferents influence the activity of midbrain DA neur ons, and intact 5-HT systems are necessary for sciatic nerve stimulati on to alter DA cell activity. However, the role that 5-HT plays in med iating peripheral sensory input remains unclear.