Presynaptic modulation of synaptic gamma-aminobutyric acid transmission bytandospirone in rat basolateral amygdala

Nystatin-perforated patch recordings were made from mechanically dissociate d neurons (in which functional native presynaptic nerve terminals are prese rved), isolated from the basolateral amygdala regions to investigate the ef fects of tandospirone on gamma -aminobutyric acidergic (GABAergic) inhibiti on. Two types of neurons, ovoid-shaped and pyramidal-shaped neurons, were o btained from the basolateral amygdala nuclei and the electrophysiological c haracteristics of these two types of neurons supported the morphological cl assification of these isolated neurons. From the ovoid-shaped neurons, bicu culline-sensitive GABA(A)ergic miniature inhibitory postsynaptic currents ( miniature IPSC) were recorded in the presence of tetrodotoxin, 6-cyano-7-ni troquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphovaleric acid (DL-AP S). Tandospirone (10 muM) reversibly and continuously inhibited the GABAerg ic miniature synaptic events to 66.3 +/- 2.1% of control (P < 0.01, n = 17) without affecting the miniature IPSC amplitude (104.0 +/- 3.1% of control, n = 17). The similar inhibition of miniature IPSC frequency was mimicked b y a specific 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetrali n (8-OH-DPAT, 1 <mu>M), and the effects of tandospirone were prevented in t he presence of a specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4- [4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190, 1 muM). Activati on of 5-HT1A receptors by 8-OH-DPAT(1 muM) evoked no direct postsynaptic ef fects in enzyme-treated isolated basolateral amygdala neurons, suggesting t hat tandospirone acts at presynaptic 5-HT1A receptors. Furthermore, this pr esynaptic inhibition by tandospirone was prevented after treatment with a p ertussis toxin-sensitive GTP-binding protein (G-protein) inhibitor, N-ethyl maleimide (at 3 muM for 5 min). In conclusion, in the basolateral amygdala nuclei, tandospirone activated presynaptic 5-HT1A receptors on the GABAergi c nerve terminals projecting to ovoid-shaped neurons and inhibited synaptic GABA transmission via G-proteins. (C) 2000 Elsevier Science B.V. All right s reserved.