DOPAMINE AGONIST-MEDIATED INHIBITION OF ACETYLCHOLINE-RELEASE IN RAT STRIATUM IS MODIFIED BY THYROID-HORMONE STATUS

K+-evoked acetyl[H-3]choline ([H-3]ACh) release was inhibited in a con centration-dependent manner by apomorphine and the D2 agonist quinpiro le in striatal slices prepared from euthyroid and hypothyroid rats. Ho wever, there was a significant increase in the maximum inhibition obse rved with both agonists in the hypothyroid compared with the euthyroid group, which paralleled the increased D2 agonist sensitivity reported for stereotyped behavior. The D2 antagonist raclopride decreased, and the D1 antagonist SCH 23390 increased, the inhibition of [H-3]ACh rel ease by apomorphine, confirming an inhibitory role for D2 receptors an d an opposing role for D1 receptors. Because there is no difference in D1 or D2 receptor concentration between the euthyroid and hypothyroid groups, it is suggested that thyroid hormone modulation of D2 recepto r sensitivity affects a receptor-mediated event. Following intrastriat al injection of pertussis toxin (PTX), apomorphine no longer inhibited [H-3]ACh release. In fact, increased [H-3]ACh release was observed, a n effect reduced by SCH 23390, providing evidence that D1 receptors en hance [H-3]ACh release, and confirming that a PTX-sensitive G protein mediates the D2 response. As it has been reported that thyroid hormone s modulate G protein expression, this mechanism may underlie their eff ect on dopamine agonist-mediated inhibition of ACh.