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The Journal of Neuroscience, January 15, 1999, 19(2):570-577

Cross-Modulation of Synaptic Plasticity by -Adrenergic and 5-HT_1A Receptors in the Rat Basolateral Amygdala

Su-Jane Wang, Li-Liang Cheng, and Po-Wu Gean

Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan 701

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 -adrenergic and serotonin 1A (5-HT_1A) receptors and to elucidate their underlying mechanisms. Stimulation of presynaptic -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 -adrenergic receptors occurs at a step downstream from cAMP production.

Key words: serotonin; isoproterenol; cAMP; protein kinase A; calcium channel; long-term potentiation; amygdala

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Copyright © 1999 Society for Neuroscience  0270-6474/99/192570-08$05.00/0

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