Trans-ACPD and L-APB presynaptically inhibit excitatory glutamatergic transmission in the basolateral amygdala (BLA).
Intracellular recordings were obtained from neurones of the basolateral nucleus of the amygdala (BLA) and glutamate-mediated EPSPs evoked by stimulation of the stria terminalis (ST). The conformationally restricted analogue of glutamate trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) caused a dose-dependent reduction in EPSP amplitude, EC50 approximately 50 microM. This effect was mimicked by the glutamate autoreceptor agonist, L-aminophosphonobutyric acid (L-APB, 50 microM). Furthermore, the effects of submaximal concentrations (50 microM) of trans-ACPD and L-APB were additive. The reduction in EPSP amplitude is observed with concentrations of both drugs that have no effect on either the resting membrane potential or the input resistance of BLA neurones. In addition, these compounds can reduce EPSP amplitude but not the response to exogenous application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA) suggesting activation of presynaptic receptors. These findings suggest that both trans-ACPD and L-APB act at presynaptic glutamate receptors on glutamatergic afferents to reduce excitatory transmission in the BLA.
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
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Shinnick-Gallagher
D000613:Aminobutyrates / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004566:Electrodes; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D000613:Aminobutyrates; D005971:Glutamates; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; C012729:2-amino-4-phosphonobutyric acid