Local GABAergic modulation of acetylcholine release from the cortex of freely moving rats

Cortical perfusion with GABA agonists and antagonists modulates the spontan eous release of cortical acetylcholine and GABA in freely moving rats. Twen ty-four hours after implantation of a dialysis fibre, cerebral cortex spont aneously released acetylcholine (3.8 +/- 0.2 pmol/10 min) and GABA (6.6 +/- 0.4 pmol/10 min) at a stable rate. Local administration of GABA (1 or 5 mM ) or the GABA(A) agonist muscimol (25 or 50 mu M) had no effect on the spon taneous release of acetylcholine. However, bicuculline (1-25 mu M), a GABA( A) antagonist, added to the dialysis perfusate, elicited a concentration-de pendent increase of acetylcholine release to approximately double that of c ontrol. This effect of bicuculline (25 mu M) was completely prevented by co perfusion with muscimol (50 mu M). Local administration of the GABA(B) rece ptor agonist baclofen (10 or 50 mu M) elicited a concentration-dependent in crease in spontaneous acetylcholine release with a maximal increase of abou t 60%. Intracortical administration of baclofen also decreased the spontane ous release of GABA. The GABA(B) receptor antagonist CGP 35348 (1 mM), admi nistered alone for 20 min through the dialysis fibre, was without effect on spontaneous acetylcholine release; however, it completely blocked both the baclofen-induced increase in acetylcholine release and the decrease in GAB A release. These results suggest that cortically released GABA exerts a ton ic influence on cholinergic activity.