NONSTRIATAL DOPAMINE D1 RECEPTORS REGULATE STRIATAL ACETYLCHOLINE-RELEASE IN-VIVO

The role of dopamine (DA) D1 receptors in the regulation of acetylchol ine (ACh) release in the striatum was studied using in vivo microdialy sis in freely moving rats. Systemic administration of the full D1 DA r eceptor agonist A-77636 (4 mu mol/kg) increased striatal ACh release b y 53% above the base line and decreased DA release by 33%. Local appli cation of A-77636 (10 and 100 mu M) by reverse dialysis was without ef fect on either striatal ACh or DA release. Systemic administration of the D1 DA receptor antagonist SCH 23390 (0.74 mu mol/kg) or SCH 39166 (1.42 mu mol/kg) blocked the stimulation of striatal ACh release produ ced by systemic A-77636 (4 mu mol/kg). Local perfusion of either SCH 2 3390 or SCH 39166 did not decrease basal ACh release. Furthermore, whe n applied locally via the dialysis probe, SCH 23390 (12 mu M) or SCH 3 9166 (50 mu M) failed to attenuate the stimulation of striatal ACh rel ease produced by systemic A-77636. Similarly, d-amphetamine (5.42 mu m ol/kg)-induced increases in striatal ACh release were not modified by simultaneous local perfusion with SCH 39166 (50 mu M). These findings are consistent with the hypothesis that D1 receptor activation stimula tes ACh release in the striatum. However, because local application of D1 receptor agonists and antagonists fail to influence ACh release, t he relevant D1 receptors are not located in the striatum. The use of u nphysiological dialysis conditions (high concentrations of acetylcholi nesterase (AChE) inhibitors, high Ca++ concentrations and an absence o f Mg++ in the perfusion fluid) may account for some earlier suggestion s that local D1 receptors regulate ACh release in the striatum.