Muscimol increases acetylcholine release by directly stimulating adult striatal cholinergic interneurons

Login, Ivan S.; Pal, Shanthi N.; Adams, Donna; Gold, Paul E.

doi:10.1016/s0006-8993(97)01051-2

Cited by 13 publications

(7 citation statements)

References 41 publications

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“…The present study shows that intra‐accumbal infusion of the GABA A receptor agonist muscimol reduced basal accumbal acetylcholine efflux in freely moving rats in a dose‐related manner. These findings were in contrast to earlier findings that muscimol enhanced spontaneous acetylcholine release from striatal slices of experimental animals (Login et al, ; Scatton & Bartholini, ; Supavilai & Karobath, ), but were in accordance with a neuropharmacologial study showing intra‐accumbally administered muscimol decreased accumbal basal extracellular acetylcholine levels in unanesthetized rats (Rada, Mark, & Hoebel, ). Pharmaco‐behavioral studies have shown that intra‐accumbally applied muscimol can suppress accumbal cholinergic neural activity‐dependent locomotion through a mechanism independent of GABA A receptor activation.…”

Section: Discussionsupporting

confidence: 73%

“…In earlier studies, GABA was considered unable to alter acetylcholine release from the nucleus accumbens in rat brain slices (Stoof, Den Breejen, & Mulder, ). The GABA A receptor agonist muscimol was shown to enhance and suppress spontaneous striatal acetylcholine release (Login, Pal, Adams, & Gold, ; Scatton & Bartholini, ; Supavilai & Karobath, ) and potassium loading‐induced striatal acetylcholine release (Supavilai & Karobath, ), respectively, from brain sections. Subsequently, GABA A receptor ligands were found to affect extracellular levels of acetylcholine in the nucleus accumbens of unanesthetized rats.…”

Section: Introductionmentioning

confidence: 99%

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In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Aono

Watanabe

Ishikawa

et al. 2018

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Cholinergic neurons in the nucleus accumbens contain GABAA and GABAB receptors that are thought to inhibit neural activity. We analyzed the roles of GABAA and GABAB receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30–60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABAA receptor agonist muscimol (3 and 30 pmol) induced a dose‐related decrease in accumbal acetylcholine. GABAB receptor agonist baclofen (30 and 300 pmol) also produced a dose‐related decrease in acetylcholine. GABAA receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)‐induced decrease in acetylcholine. GABAB receptor antagonist 2‐hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)‐induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2‐hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABAA and GABAB receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Aono

Watanabe

Ishikawa

et al. 2018

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“…anaesthetic agents were shifted only about threefold. In addition, muscimol, a GABA A receptor agonist, inhibited the release by about 25% with an EC 50 consistent with previous reports (Login et al 1998). These data imply that, in this experimental paradigm, full activation of GABA A receptors may produce a small inhibition of release.…”

Section: Discussionsupporting

confidence: 91%

Inhibitory effects of intravenous anaesthetic agents on K + -evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca 2+ channels and GABA A receptors

Kitayama

Hirota

Kudo

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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It is widely accepted that most general anaesthetic agents depress the central nervous system (CNS) by potentiation or activation of the GABA(A) receptor-mediated Cl(-) conductance. These agents also reportedly inhibit voltage-sensitive Ca(2+) channels (VSCCs), thus depressing excitatory transmission in the CNS. However, in this regard there are few functional data at the level of neurotransmitter release. In this study we examined the effects of VSCC antagonists and a range of intravenous anaesthetic agents on K(+)(40 mM)-evoked glutamate release from rat cerebrocortical slices in the absence and presence of the GABA(A) receptor antagonist bicuculline (100 microM). We employed both selective and non-selective VSCC antagonists, the anaesthetic barbiturates thiopental, pentobarbital and phenobarbital, the non-anaesthetic barbiturate barbituric acid, the non-barbiturate anaesthetics alphaxalone, propofol and ketamine and the GABA(A) receptor agonist, muscimol. Glutamate released into the incubation medium was determined by a glutamate dehydrogenase-coupled assay. Omega-agatoxin IV(A) (P-type VSCC), omega-conotoxin MVII(C) (P/Q-type VSCC) and Cd(2+) (non-selective) essentially abolished glutamate release whilst nifedipine (L-type VSCC) and omega-conotoxin GVI(A) (N-type VSCC) reduced release by less than 30%. The concentrations producing 50% of the maximum inhibition (IC(50)) for thiopental, pentobarbital, phenobarbital, alphaxalone, propofol and ketamine were (in microM) 8.3, 22, 112, 6.3, 83 and 120, respectively. Barbituric acid produced a small (about 20%) inhibition. With the exception of ketamine, the IC(50) values for these anaesthetic agents were increased threefold by bicuculline (100 microM). In addition, muscimol significantly inhibited release by 26% with an IC(50) of 1.1 microM. In summary, a range of anaesthetic agents at clinically achievable concentrations inhibit glutamate release and this inhibition of release appears to be due mainly to direct inhibition of P/Q-type VSCCs, although activation of the GABA(A) receptor plays a role in this response.

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“…, 1998). In the rat striatum, opposite results have been obtained as GABA‐A receptors have been shown to increase (Scatton & Bartholini, 1980; Login et al. , 1998) or inhibit (Anderson et al.…”

Section: Discussionmentioning

confidence: 97%

Presynaptic GABA‐A receptors prevent depression of nicotinic transmission in rabbit coeliac ganglion neurones

Ercoli¹,

Miolan²,

Niel³

et al. 2007

Eur J of Neuroscience

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We investigated the involvement of GABA-A receptors in the modulation of the nicotinic transmission of central origin in isolated rabbit coeliac ganglia. Our study was performed in vitro and the electrical activity of the ganglionic neurones was recorded using intracellular recording techniques. During iterative stimulation of the splanchnic nerves, the synaptic action potential probability decreased gradually, indicating a depression of the nicotinic activation. Pharmacological agents acting at GABA-A receptors modulated the action potential probability during the train of pulses. Muscimol (a GABA-A receptor agonist), diazepam (a benzodiazepine site agonist) and 1-[2-[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (a GABA uptake blocker) increased this probability. Conversely, gabazine or bicuculline (two GABA-A receptor antagonists), picrotoxin (a picrotoxin site agonist) and flumazenil (a benzodiazepine site antagonist) reduced it. These results demonstrate that endogenous GABA, released during the train of pulses, facilitates the central nicotinic activation of the ganglionic neurones by acting on GABA-A receptors. Muscimol also reduced the amplitude ratio of excitatory postsynaptic potentials triggered during the paired-pulse protocol without any change in postsynaptic properties. This result is consistent with a presynaptic action of GABA-A receptors. Our study shows that presynaptic GABA-A receptors facilitate the central nicotinic activation of prevertebral ganglionic neurones and thus play a novel role in the integrative properties of the sympathetic prevertebral ganglia.

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Muscimol increases acetylcholine release by directly stimulating adult striatal cholinergic interneurons

Cited by 13 publications

References 41 publications

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Inhibitory effects of intravenous anaesthetic agents on K + -evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca 2+ channels and GABA A receptors

Presynaptic GABA‐A receptors prevent depression of nicotinic transmission in rabbit coeliac ganglion neurones

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Muscimol increases acetylcholine release by directly stimulating adult striatal cholinergic interneurons

Cited by 13 publications

References 41 publications

In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

Inhibitory effects of intravenous anaesthetic agents on K + -evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca 2+ channels and GABA A receptors

Presynaptic GABA‐A receptors prevent depression of nicotinic transmission in rabbit coeliac ganglion neurones

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In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

In vivo neurochemical evidence that stimulation of accumbal GABA_A and GABA_B receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats