PHARMACOLOGY OF SENSORY STIMULATION-EVOKED INCREASES IN FRONTAL CORTICAL ACETYLCHOLINE-RELEASE

Recent research has demonstrated that a variety of sensory stimuli can increase acetylcholine release in the frontal cortex of rats. The aim of the present experiments was to investigate the pharmacological reg ulation of sensory stimulation-induced increases in the activity of ba sal forebrain cholinergic neurons. To this end, the effects of agonist s and antagonists at a variety of neurotransmitter receptors on basal and tactile stimulation-evoked increases in frontal cortical acetylcho line release were studied using in vivo brain microdialysis. Tactile s timulation, produced by gently stroking the rat's neck with a nylon br ush for 30 min, significantly increased frontal cortical acetylcholine release by more than 100% above baseline. The noradrenergic alpha(2) agonist clonidine (0.1 or 0.2 mg/kg) and alpha(1) antagonist prazosin (1 mg/kg) failed to affect basal cortical acetylcholine release; howev er, both compounds significantly reduced the increases evoked by senso ry stimulation. In contrast, the alpha(2) antagonist yohimbine (3 mg/k g) increased basal cortical acetylcholine release, thereby preventing meaningful investigation of its effects on tactile stimulation-evoked increases. The benzodiazepine agonist diazepam (5 mg/kg) reduced, and the GABA(A) receptor antagonist picrotoxin (2 mg/kg) increased basal c ortical acetylcholine release; in addition, diazepam attenuated the in creases in cortical acetylcholine release evoked by tactile stimulatio n. While dopaminergic D-1 (SCH 23390, 0.15 mg/kg) and D-2 (raclopride, 1 mg/kg) receptor antagonists did not by themselves significantly inf luence the increases evoked by tactile stimulation, their co-administr ation produced a significant reduction. The opioid receptor antagonist naltrexone (1.5 mg/kg) failed to affect either basal or tactile stimu lation-evoked increases in acetylcholine overflow. Finally, the non-co mpetitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleat e (MK-801; 0.025 and 0.05 mg/kg) increased basal cortical acetylcholin e release. These results confirm that cortically projecting cholinergi c neurons are activated by sensory stimuli, and indicate that the incr eases in cortical acetylcholine release produced by tactile stimulatio n are inhibited by stimulation of a, or blockade of a, noradrenergic r eceptors, and by enhanced GABAergic transmission. In addition, simulta neous blockade of dopamine D-1 and D-2 receptors appears necessary to achieve a significant reduction of sensory stimulation-evoked acetylch oline release in the frontal cortex. The results are consistent with t he hypothesis that cortical acetylcholine release is a component of th e neurochemistry of arousal and/or attention and indicate that this is modulated by GABAergic, noradrenergic and dopaminergic systems. In co ntrast, endogenous opioid actions do not appear to be involved. (C) 19 98 IBRO. Published by Elsevier Science Ltd.