RECEPTOR SUBTYPE-SPECIFIC EFFECTS OF GABA AGONISTS ON NEURONS RECEIVING AORTIC DEPRESSOR NERVE INPUTS WITHIN THE NUCLEUS OF THE SOLITARY TRACT

The inhibitory amino acid gamma amino butyrate (GABA) has been shown t o profoundly alter the integration of arterial baroreceptor inputs wit hin the nucleus of the solitary tract (NTS). However, the relative rol es of the major GABA receptor subtypes, the GABA(A) and the GABA(B) re ceptors, in the modulation of monosynaptic compared to polysynaptic af ferent transmission within the NTS remain uncharacterized. In anesthet ized rats, three types of NTS neuron were identified by their response s to aortic depressor nerve (ADN) stimulation; monosynaptic neurons (M SNs), polysynaptic neurons (PSNs) and ADN non-evoked neurons (NENs). S elective GABA(A) and GABA(B) agonists were applied to these neurons us ing iontophoretic techniques. The endogenous ligand GABA (2 mM), the s elective GABA(A) agonist muscimol (0.04 and 0.02 mM) and the GABA(B) a gonist baclofen (10 mM) all inhibited the spontaneous discharge of MSN s, PSNs and NENs (P < 0.01 for each group). In addition, GABA, muscimo l and baclofen also inhibited ADN evoked discharge in both MSNs and PS Ns (P < 0.05 for each group). Both GABA and baclofen significantly inh ibited ADN evoked discharge in PSNs to a greater extent than in MSNs ( P < 0.05 fur each comparison). Muscimol at both doses, however, simila rly inhibited ADN evoked discharge in both MSNs and PSNs. Examination of action potential amplitude and co-iontophoretic application of glut amate and GABA agonists suggested that GABA and muscimol induced inhib ition were likely to be post-synaptic in origin, while baclofen produc ed both pre-synaptic and post-synaptic inhibition, depending upon the cell. In conclusion, GABA can influence baroreceptor afferent integrat ion through both pre-synaptic and post-synaptic mechanisms. Furthermor e, the effects of GABA(B) agonists are variable depending upon the lev el of afferent integration, with MSNs being generally less sensitive t han PSNs. (C) 1998 Elsevier Science B.V. All rights reserved.