title: Pharmacology of sensory stimulation-evoked increases in frontal cortical acetylcholine release.
abstract: 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 regulation of sensory stimulation-induced increases in the activity of basal forebrain cholinergic neurons. To this end, the effects of agonists and antagonists at a variety of neurotransmitter receptors on basal and tactile stimulation-evoked increases in frontal cortical acetylcholine release were studied using in vivo brain microdialysis. Tactile stimulation, produced by gently stroking the rat's neck with a nylon brush for 20 min, significantly increased frontal cortical acetylcholine release by more than 100% above baseline. The noradrenergic alpha2 agonist clonidine (0.1 or 0.2 mg/kg) and alpha1 antagonist prazosin (1 mg/kg) failed to affect basal cortical acetylcholine release; however, both compounds significantly reduced the increases evoked by sensory stimulation. In contrast, the alpha2 antagonist yohimbine (3 mg/kg) 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 cortical acetylcholine release; in addition, diazepam attenuated the increases in cortical acetylcholine release evoked by tactile stimulation. While dopaminergic D1 (SCH 23390, 0.15 mg/kg) and D2 (raclopride, 1 mg/kg) receptor antagonists did not by themselves significantly influence the increases evoked by tactile stimulation, their co-administration produced a significant reduction. The opioid receptor antagonist naltrexone (1.5 mg/kg) failed to affect either basal or tactile stimulation-evoked increases in acetylcholine overflow. Finally, the non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (MK-801; 0.025 and 0.05 mg/kg) increased basal cortical acetylcholine release. These results confirm that cortically projecting cholinergic neurons are activated by sensory stimuli, and indicate that the increases in cortical acetylcholine release produced by tactile stimulation are inhibited by stimulation of alpha2 or blockade of alpha1 noradrenergic receptors, and by enhanced GABAergic transmission. In addition, simultaneous blockade of dopamine D1 and D2 receptors appears necessary to achieve a significant reduction of sensory stimulation-evoked acetylcholine release in the frontal cortex. The results are consistent with the hypothesis that cortical acetylcholine release is a component of the neurochemistry of arousal and/or attention and indicate that this is modulated by GABAergic, noradrenergic and dopaminergic systems. In contrast, endogenous opioid actions do not appear to be involved.
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Acquas
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.forename: H C
authors.initials: HC
authors.lastname: Fibiger
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012677:Sensation / Q000502:physiology*; D014110:Touch / Q000502:physiology
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D018492:Dopamine Antagonists; D018755:GABA Agonists; D009292:Narcotic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D000109:Acetylcholine