SEROTONIN DEPRESSES EXCITATORY SYNAPTIC TRANSMISSION AND DEPOLARIZATION-EVOKED CA2-HT1A RECEPTORS( INFLUX IN RAT BASOLATERAL AMYGDALA VIA 5)

The actions of serotonin on rat basolateral amygdala neurons were stud ied with conventional intracellular recording techniques and fura-e fl uorimetric recordings. Bath application of 5-hydroxytryptamine (5-HT o r serotonin) reversibly suppressed the excitatory postsynaptic potenti al in a concentration-dependent manner without affecting the resting m embrane potential and neuronal input resistance. Extracellular Ba2+ or pertussis toxin pretreatment did not affect the depressing effect of 5-HT suggesting that it is not mediated through activation of G(i/o), protein-coupled K+ conductance, The sensitivity of postsynaptic neuron s to glutamate receptor agonist was unaltered by the 5-HT pretreatment , In addition, the magnitude of paired-pulse facilitation was increase d in the presence of 5-HT indicating a presynaptic mode of action. The effect of 5-HT was mimicked by the selective 5-HT1A agonist 8-hydroxy -dipropylaminotetralin (8-OH-DPAT) and was blocked by the selective 5- HT1A antagonist methoxyphenyl)-4[4-(2-phthalimido)butyl]piperazine oxa diazol-3-yl]methyl]phenyl]-methanesulphonamide. In contrast, the selec tive 5-HT2 receptor antagonist ketanserin failed to affect the action of 5-MT. The effects of 5-HT and 8-OH-DPAT on the high K+-induced incr ease in [Ca2+](i) were studied in acutely dissociated basolateral amyg dala neurons. High K+-induced increase in [Ca2+](i) was blocked by Ca2 +-free solution and Cd2+ suggesting that Ca2+ entry responsible for th e depolarizaton-evoked increase in [Ca2+](i) occurred through voltage- dependent Ca2+ channels. Application of 5-HT and 8-OH-DPAT reduced the K+-induced Ca2+ influx in a concentration-dependent manner. The effec t of 5-HT was completely abolished in slices pretreated with Rp-cyclic adenosine 3',5'-monophosphothioate (Rp-cAMP), a regulatory site antag onist of protein kinase A, suggesting that 5-HT may act through a cAMP -dependent mechanism. Taken together, these results suggest that funct ional 5-HT1A receptors are present in the excitatory terminals and med iate the 5-HT inhibition of synaptic transmission in the amygdala.