Presynaptic modulation of synaptic γ-aminobutyric acid transmission by tandospirone in rat basolateral amygdala

Abstract

Nystatin-perforated patch recordings were made from mechanically dissociated neurons (in which functional native presynaptic nerve terminals are preserved), isolated from the basolateral amygdala regions to investigate the effects of tandospirone on γ-aminobutyric acidergic (GABAergic) inhibition. Two types of neurons, ovoid-shaped and pyramidal-shaped neurons, were obtained from the basolateral amygdala nuclei and the electrophysiological characteristics of these two types of neurons supported the morphological classification of these isolated neurons. From the ovoid-shaped neurons, bicuculline-sensitive GABA Aergic miniature inhibitory postsynaptic currents (miniature IPSC) were recorded in the presence of tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dl-2-amino-5-phosphovaleric acid ( dl-AP5). Tandospirone (10 μM) reversibly and continuously inhibited the GABAergic 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 by a specific 5-HT 1A receptor agonist 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT, 1 μM), and the effects of tandospirone were prevented in the presence of a specific 5-HT 1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190, 1 μM). Activation of 5-HT 1A receptors by 8-OH-DPAT (1 μM) evoked no direct postsynaptic effects in enzyme-treated isolated basolateral amygdala neurons, suggesting that tandospirone acts at presynaptic 5-HT 1A receptors. Furthermore, this presynaptic inhibition by tandospirone was prevented after treatment with a pertussis toxin-sensitive GTP-binding protein (G-protein) inhibitor, N-ethylmaleimide (at 3 μM for 5 min). In conclusion, in the basolateral amygdala nuclei, tandospirone activated presynaptic 5-HT 1A receptors on the GABAergic nerve terminals projecting to ovoid-shaped neurons and inhibited synaptic GABA transmission via G-proteins.