PHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE RECEPTORS MODULATEDOPAMINE RELEASE IN RAT HIPPOCAMPUS AND STRIATUM

The effects of infusing the glutamate receptor agonist pha-amino-3-hyd roxy-5-methyl-4-isoxazolepropionate (AMPA) on the release of dopamine (DA) has been studied in rat hippocampus and striatum in vivo. In hipp ocampus, AMPA (1-10 mu M) produced a dose related increase in dialysat e DA, but at 100 mu M AMPA a sustained decrease in extracellular DA wa s observed. However, when samples were collected at 5-min intervals 10 0 mu M AMPA infusion revealed a brief increase in hippocampal dialysat e DA. Infusion of 100 mu M AMPA and 500 mu M diazoxide, which blocks A MPA receptor desensitization, led to a marked increase in extracellula r DA, as did diazoxide alone, although to a lesser extent. The AMPA re ceptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione (CNQX; 200 mu M) reversed the effect of AMPA and/or diazoxide infusion on dialysate DA and when infused alone, CNQX also decreased hippocampal dialysate D A. AMPA (50-500 mu M) increased striatal DA release. The effect of AMP A on extracellular DA was reversed by CNQX (200 mu M). Diazoxide infus ion caused a decrease in striatal DA release, and this was not affecte d by CNQX. These data suggest that hippocampal, but not striatal AMPA receptor desensitization may play a role in regulating DA release.