Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors.

Serotonin (5-HT) nerve terminals innervate sympathetic preganglionic neurons of the intermediolateral cell column (IML); however, neither the depolarization-induced release of 5-HT nor the presence of presynaptic modulatory autoreceptors have been directly studied in this system. We used in vitro superfusion of the microdissected intermediate area (including the intermediolateral cell column, intercalated nucleus, and central autonomic nucleus) of the rat thoracic spinal cord to measure basal and stimulated release of preloaded [3H]5-HT. Elevated K+ evoked a concentration- and Ca(2+)-dependent release of [3H]5-HT. Exogenous 5-HT and the 5-HT1B agonist, CGS-12066B, both decreased the K(+)-stimulated release of [3H]5-HT. A 5-HT1B antagonist (methiothepin) blocked the 5-HT- and the CGS-12066B-induced inhibition of K(+)-evoked release of [3H]5-HT. A 5-HT1A antagonist (NAN-190) did not alter the inhibitory actions of exogenous 5-HT. Moreover, a 5-HT1A agonist (8-OH-DPAT), a 5-HT2A/2C agonist [(+/-)-DOI hydrochloride), and a 5-HT3 agonist (2-methyl-5-HT) did not alter the K(+)-evoked release of [3H]5-HT. These data demonstrate that 5-HT is released from the intermediate area of the rat thoracic spinal cord. The 5-HT receptor subtype involved in the inhibition of the evoked release of [3H]5-HT is of the 5-HT1B subtype. These findings may help clarify the complex role of 5-HT in spinal regulation of the sympathetic nervous system.