Muscarinic and GABA_A receptors modulate acetylcholine release in feline basal forebrain

Abstract

Acetylcholine (ACh) release within the basal forebrain changes significantly as a function of sleep and wakefulness, hence identifying the neurochemical modulators of basal forebrain ACh release will contribute to a mechanistic understanding of sleep cycle regulation. This study tested the hypothesis that muscarinic and gamma aminobutyric acid(A) (GABAA) receptors modulate basal forebrain ACh release. Cats were anaesthetized with halothane to hold arousal state constant and a microdialysis probe was aimed stereotaxically for the substantia innominata region of the basal forebrain. Four concentrations of the muscarinic antagonist scopolamine (0.1, 0.3, 1.0, and 10 nm) and five concentrations of the GABAA antagonist bicuculline (3, 10, 30, 100, and 300 micro m) were delivered by reverse dialysis from the same probes used to collect ACh. These results are based on 27 experiments in nine animals. Scopolamine and bicuculline each caused a concentration dependent enhancement of ACh release. Scopolamine increased ACh by 118% above control levels whereas bicuculline was more effective, causing a 287% increase in ACh release. Scopolamine was more potent (EC50 = 0.16 nm) than bicuculline (EC50 > or = 90 micro m) for increasing ACh release. The results support the hypothesis that substantia innominata ACh release is modulated by muscarinic autoreceptors and inhibited by GABAA receptors. These findings are consistent with the interpretation that inhibition of basal forebrain cholinergic neurotransmission by GABA contributes to the generation of sleep.

Anti-amnesic activity of Citrus aurantium flowers extract against scopolamine-induced memory impairments in rats

“…The cognition-enhancing agents activate cholinergic transmission via an agonistic or antagonistic effect on GABA A /benzodiazepine receptor and GABA A /benzodiazepine receptor complex controls acetylcholine release [23].…”

5-HT Receptor Regulation of Neurotransmitter Release

“…5-HT Receptor WAY 161503, 8,9-dichloro-2,3,4,4-tetrahydro-1H-pyrazino͓1,2-a͔quinoxalin-5(6H)-one hydrochloride (5-HT 2C agonist); SR 57227, 1-(6-chloro-2-pyridinyl)-4-piperidinamine hydrochloride (5-HT 3 agonist); Y-25130, N-1-azabicyclo͓2.2.2͔-oct-3-yl-6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxamide hydrochloride (azasetron; 5-HT 3 antagonist); ML10302, 2-(1-piperidinyl)ethyl-4-amino-5-chloro-2-methoxybenzoate (5-HT 4 agonist); RS 39604, 1-͓4-amino-5-chloro-2- (3,5-dimethoxyphenyl) 1998; Vazquez and Baghdoyan, 2003), dopaminergic (Ronken et al, 1993;Steiniger and Kretschmer, 2003), and noradrenergic neurons (Fung and Fillenz, 1983;Suzdak and Gianutsos, 1985;Tanaka et al, 2002;Sakamaki et al, 2004;Ushigome et al, 2004) Presynaptic 5-HT heteroreceptors play mainly a physiological role in the local fine regulation of the release of the transmitter from the axon terminal on which the receptors are located. They inhibit or facilitate transmitter release in response to action potentials invading the varicosities.…”

Dynamic changes in GABAAreceptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

“…The cholinergic cells also express c-Fos following continuous waking imposed by sleep deprivation (SD), whereas they do not express c-Fos following sleep in control (SC) or recovery (SR) conditions, comprised of >75% sleep of which ~90% is quiet, NREM sleep [5]. Their inactivity during NREM sleep could be imposed through inhibition by GABA [6,7] that can be released from co-distributed BF GABAergic neurons which discharge in association with slow wave activity [8-10] and express c-Fos in association with sleep [5]. …”