Cross-modulation of synaptic plasticity by β-adrenergic and 5-HT(1A) receptors in the rat basolateral amygdala

Abstract

Neurotransmitter receptors are often colocalized in a neuron with other receptors, and activation of one receptor can either amplify or antagonize the response to a colocalized receptor. The aim of this study was to investigate the cross-regulation of synaptic transmission by β-adrenergic and serotonin 1A (5-HT(1A)) receptors and to elucidate their underlying mechanisms. Stimulation of presynaptic β-adrenergic receptors with isoproterenol (Iso) in the basolateral amygdala resulted in a long-lasting increase in synaptic transmission. This effect was mimicked by forskolin, an activator for adenylyl cyclase and a cAMP analog. In addition, the effect of forskolin was blocked by catalytic and regulatory site antagonists for cAMP- dependent protein kinase (PKA), indicating a PKA-mediated mechanism. Application of 5-HT depressed the synaptic transmission and blocked Iso- and forskolin-induced potentiation. The effect of 5-HT was mimicked by the selective 5-HT(1A) agonist 8-hydroxy-dipropylaminotetralin and was blocked by the selective 5-HT(1A) antagonist 1-(2-methoxyphenyl)-4[4-(2- phthalimido)butyl]piperazine, indicating its mediation by 5-HT(1A) receptors. To determine the locus of interaction, Sp-cAMPS, a membrane-permeable activator of PKA, was applied, and the potentiation produced by Sp-cAMPS was completely blocked in slices pretreated with 5-HT. These results suggest that the interaction between the intracellular signaling pathways activated by 5- HT(1A) and β-adrenergic receptors occurs at a step downstream from cAMP production.