Serotonin and GABA-induced depolarizations of frog primary afferent fibers

Abstract

The interaction of γ-aminobutyric acid (GABA) and serotonin (5-HT) on primary afferent terminals of the isolated frog spinal cord was investigated by sucrose gap recordings from dorsal roots. Application of 5-HT (1.0–100 μM) to the Ringer's solution significantly reduced afferent terminal depolarizations elicited by concentrations of GABA ranging from 0.1 to 1.0 mM. The reductions of GABA-depolarizations which were produced by 1.0 μM 5-HT were mimicked by the 5-HT 1A agonists 8-OH-DPAT (8-hydroxy-2-( n-dipropylamino)tetralin) and ipsapirone. The effects of ipsapirone were reversed by the 5-HT 1A antagonists spiperone. The decreases of GABA-depolarizations produced by high doses of 5-HT were duplicated by application of α-methyl-5-HT 1 c/2 agonist and reversed by superfusion of the cord with mianserin, a 5-HT 1C/2 antagonist. The presumptive 5-HT 1A receptor-mediated effects of 1.0 μM 5-HT and 8-OH-DPAT appeared to result from a direct action on afferent terminals because the reduction of GABA responses was unchanged by addition of TTX to the Ringer's solution. In contrast, the putative 5-HT 1C/2 receptor actions of 100 μM 5-HT and α-methyl-5-HT were substantially reduced by TTX and are presumably caused by activation of receptors located on interneurons. GABA B receptors did not appear to be affected by addition of 5-HT at low or high concentrations because baclofen-induced afferent terminal hyperpolarizations remained unchanged during exposure to 5-HT. The effects of 5-HT on GABA-depolarizations were not caused by changes in GABA uptake or changes in the rate of desensitization of GABA receptors because: (1) afferent terminal depolarizations produced by the non-transportable GABA A receptor agonist muscimol were significantly reduced by 8-OH-DPAT and (2) the decrement in depolarization produced by repetitive exposure to GABA, which is caused by both ‘receptor’ desensitization and by neuronal transport of GABA, was unaffected by 5-HT. These observations are important in understanding the action of 5-HT on transmission of sensory information by afferent fibers.