Serotonin depresses excitatory synaptic transmission and depolarization‐evoked Ca2+ influx in rat basolateral amygdala via 5‐HT1A receptors

The actions of serotonin on rat basolateral amygdala neurons were studied with conventional intracellular recording techniques and fura-2 fluorimetric recordings. Bath application of 5-hydroxytryptamine (5-HT or serotonin) reversibly suppressed the excitatory postsynaptic potential in a concentration-dependent manner without affecting the resting membrane 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 neurons to glutamate receptor agonist was unaltered by the 5-HT pretreatment. In addition, the magnitude of paired-pulse facilitation was increased in the presence of 5-HT indicating a presynaptic mode of action. The effect of 5-HT was mimicked by the selective 5-HT_1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was blocked by the selective 5-HT_1A antagonist 1-(2-methoxyphenyl)-4[4-(2-phthalimido)butyl]piperazine oxadiazol-3-yl]methyl]phenyl]methanesulphonamide. In contrast, the selective 5-HT₂ receptor antagonist ketanserin failed to affect the action of 5-HT. The effects of 5-HT and 8-OH-DPAT on the high K₊-induced increase in [Ca₂₊]_i were studied in acutely dissociated basolateral amygdala neurons. High K₊-induced increase in [Ca₂₊]_i was blocked by Ca₂₊-free solution and Cd₂₊ suggesting that Ca₂₊ entry responsible for the 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 effect of 5-HT was completely abolished in slices pretreated with Rp-cyclic adenosine 3′,5′-monophosphothioate (Rp-cAMP), a regulatory site antagonist of protein kinase A, suggesting that 5-HT may act through a cAMP-dependent mechanism. Taken together, these results suggest that functional 5-HT_1A receptors are present in the excitatory terminals and mediate the 5-HT inhibition of synaptic transmission in the amygdala. Introduction