DIFFERENTIAL ACTIONS OF SEROTONIN, MEDIATED BY 5-HT1B AND 5-HT2C RECEPTORS, ON GABA-MEDIATED SYNAPTIC INPUT TO RAT SUBSTANTIA-NIGRA PARS RETICULATA NEURONS IN-VITRO

The ability of serotonin to modulate GABA-mediated synaptic input to s ubstantia nigra pars reticulata (SNr) neurons was investigated with th e use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABA(A) receptor-mediated synaptic currents (IPSCs) were attenuated reversibly similar to 60% by serotonin, which also caused a n inward current with reversal potential of -25 mV. This inward curren t was blocked by the 5-HT2 receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT1B receptor antagonist pindolo l. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABA(B) recepto r agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tet rodotoxin-sensitive GABA(A) synaptic currents (sIPSCs) were increased in frequency by serotonin (an action that was sensitive to ritanserin, but not pindolol) but reduced in frequency by baclofen. SNr neurons t herefore receive inhibitory synaptic input mediated by GABA(A) recepto rs from at least two distinct sources. One, probably originating from the striatum, may he depressed via presynaptic 5-HT1B and GABA(B) rece ptors. The second is likely to arise from axon collaterals of SNr neur ons themselves and is facilitated by an increase in firing via postsyn aptic, somatodendritic 5-HT2C receptor activation, but it is depressed by GABA(B) receptor activation. Thus, serotonin can both depolarize a nd disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectivel y, but excitation may be limited by GABA released from axon collateral s.