Differential Actions of Serotonin, Mediated by 5-HT_1Band 5-HT_2CReceptors, on GABA-Mediated Synaptic Input to Rat Substantia Nigra Pars Reticulata Neurons<i>In Vitro</i>

<jats:p>The ability of serotonin to modulate GABA-mediated synaptic input to substantia nigra pars reticulata (SNr) neurons was investigated with the use of whole-cell patch-clamp recording from slices of rat midbrain. Fast evoked GABA<jats:sub>A</jats:sub>receptor-mediated synaptic currents (IPSCs) were attenuated reversibly ∼60% by serotonin, which also caused an inward current with reversal potential of −25 mV. This inward current was blocked by the 5-HT<jats:sub>2</jats:sub>receptor antagonist ritanserin, whereas the IPSC depression was blocked by the 5-HT<jats:sub>1B</jats:sub>receptor antagonist pindolol. The amplitude ratio of IPSC pairs (50 msec interpulse interval) was enhanced by serotonin (in ritanserin) and also by the GABA<jats:sub>B</jats:sub>receptor agonist baclofen (which also depressed the IPSC), consistent with a presynaptic site of action in both cases. In contrast, spontaneous tetrodotoxin-sensitive GABA<jats:sub>A</jats:sub>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 therefore receive inhibitory synaptic input mediated by GABA<jats:sub>A</jats:sub>receptors from at least two distinct sources. One, probably originating from the striatum, may be depressed via presynaptic 5-HT<jats:sub>1B</jats:sub>and GABA<jats:sub>B</jats:sub>receptors. The second is likely to arise from axon collaterals of SNr neurons themselves and is facilitated by an increase in firing via postsynaptic, somatodendritic 5-HT<jats:sub>2C</jats:sub>receptor activation, but it is depressed by GABA<jats:sub>B</jats:sub>receptor activation. Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT<jats:sub>2C</jats:sub>and 5-HT<jats:sub>1B</jats:sub>receptors, respectively, but excitation may be limited by GABA released from axon collaterals.</jats:p>