Effects of AMPA and D1 receptor activation on striatal and nigral GABA efflux

The ability of locally-administered AMPA and D1 receptor ligands to modulate in vivo striatal and nigral GABA efflux was determined in awake, intact male rats using a dual-probe microdialysis technique. Intrastriatal perfusion of AMPA (100 microM) produced a 50-100% increase in striatal GABA efflux that was totally blocked by co-perfusion with TTX (10.0 microM). This AMPA-stimulated, TTX-sensitive GABA efflux was similar across repeated dialsysis perfusions. The effects of intrastriatal perfusion of the full D1-like agonist SKF 81297 were complex. Perfusion of the higher dose (100 microM) of SKF 81297 enhanced GABA efflux, whereas perfusion of the lower dose (10 microM) decreased GABA efflux. Both of these effects were blocked by co-perfusion with the D1-like antagonist SCH 23390 (10 microM). Intrastriatal perfusion of AMPA (100 microM), SKF 81297 (100 microM), or AMPA + SKF 81297 did not stimulate GABA efflux in the substantia nigra. These bidirectional effects of D1 agonists and the apparent dissociation, under certain conditions, between striatal and nigral GABA efflux highlight the complexities of DA- and Glu-modulated striatonigral activity in situ.