Maione, S., Rossi, F., Biggs, C.S., Fowler, L.J. and Whitton, P.S. (1997) AMPA receptors modulate extracellular 5-hydroxytryptamine concentration and metabolism in rat striatum in vivo. Neurochemistry International, 30 (3). pp. 299-304. 10.1016/S0197-0186(96)00101-5.
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We have investigated the effects of infusing the excitatory amino acid agonist α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on extracellular levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindoleacetic acid (5-HIAA) in rat striatum using in vivo microdialysis. AMPA (50-500 μM) caused a concentration-dependent increase in extracellular 5-HT, while having the converse effect on 5-HIAA. At the highest agonist dose the decrease in dialysate 5-HIAA was followed by a significant increase in this metabolite. Two hundred micromolar 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non-NMDA glutamate receptor antagonist, reversed the effects of a 100 μM AMPA on dialysate 5-HT and 5-HIAA. Co-infusion of AMPA with tetrodotoxin (TTX) abolished the effects of 100 μM AMPA, but only partially reversed the effect of 500 μM AMPA on 5-HT release. We have also investigated whether AMPA receptor desensitization, a well documented event, plays a role in AMPA receptor modulation of striatal 5-HT release. Diazoxide (500 μM), a drug which prevents AMPA receptor desensitization, failed to augment the effect of 100 μM AMPA on 5-HT release. Diazoxide alone significantly decreased 5-HT release, as did the drug cromakalim (100 μM), probably as a result of their common action as activators of ATP-dependent K+ channels. It is concluded that AMPA receptors play a role in regulating both 5-HT release and metabolism in rat striatum. However, AMPA receptor desensitization does not appear to play a role in this process in this structure.
|Departments, units and centres:||Department of Pharmacology > Department of Pharmacology|
|Journal or Publication Title:||Neurochemistry International|
|Deposited By:||Library Staff|
|Deposited On:||27 Apr 2012 17:28|
|Last Modified:||27 Apr 2012 17:28|
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