Mecamylamine blockade of nicotine enhanced noradrenaline turnover in rat brain

Morgan, W. W.; Pfeil, Karla A.

doi:10.1016/0024-3205(79)90212-1

Cited by 29 publications

(5 citation statements)

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“…These effects of (-)-nicotine were blocked by pretreatment with MEC, a centrally acting nicotinic channel blocker, but not by pretreatment with HEX, a peripherally acting nicotinic channel blocker, suggesting that the ability of (-)-nicotine to affect monoamine turnover was mediated by central nACh-R. With regard to the effects on NA and DA turnover, the present results are consistent with previous studies (Morgan and Pfeil 1979;Andersson et al 1979;Roth et al 1982;Kubo et al 1989). In contrast, (-)-nicotine increased brain 5-HT turnover at a low dose (0.04 mg/kg SC), but decreased it at a high dose (1.0 mg/kg) at 30 rain after administration in the present study.…”

Section: Discussionsupporting

confidence: 94%

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Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

et al. 1997

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The aim of the present study was to evaluate the effects of nicotinic acetylcholine receptor (nACh-R) agonists such as (-)-nicotine and related compounds on brain monoamine turnover. A single administration of (-)-nicotine (0.04, 0.2, 1.0, and 5.0 mg/kg SC) increased both noradrenaline (NA) and dopamine (DA) turnover in a dose-dependent manner, and the maximum effects were achieved 30 min after treatment with (-)-nicotine (1.0 mg/kg). The effect of (-)-nicotine on serotonin (5-HT) turnover was complicated; 5-HT turnover was increased at a low dose of (-)-nicotine (0.04 mg/kg) but decreased at a high dose (1.0 mg/kg). The (-)-nicotine (1.0 mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg i.p.) but not by hexamethonium (2.0 mg/kg i.p.). These findings indicate that systemically administered (-)-nicotine can enhance brain NA and DA turnover and affect 5-HT turnover, both of which are mediated by central nACh-R. The changes in the monoamine turnover induced by (+/-)-anabasine were similar to those induced by (-)-nicotine, while (-)-lobeline and (-)-cytisine had little effect, and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) increased NA and 5-HT turnover but not DA turnover at all doses tested. (S)-3-Methyl-5-(l-methyl-2- pyrrolidinyl)isoxazole (ABT-418), a selective neuronal nACh-R agonist, increased NA, DA and 5-HT turnover, but had a weaker effect on DA turnover than NA and 5-HT turnover. In addition, 9-amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholine esterase inhibitor, also increased monoamine turnover in the brain. Pretreatment with mecamylamine completely blocked the THA-induced increase in NA and 5-HT turnover, but not in DA turnover, suggesting that the nACh-R system is involved in the THA-induced increase in brain NA and 5-HT turnover. On the other hand, (-)-cytisine, a partial agonist for the beta 2 subunit containing nACh-R, completely inhibited the nACh-R agonist- and THA-induced increases in NA turnover, but not in DA turnover, and normalized the changes in 5-HT turnover. In conclusion, the subtypes of nACh-Rs mediating DA turnover may be different from those mediating NA and 5-HT turnover in the CNS.

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Section: Discussionsupporting

confidence: 94%

“…Brain catecholamine turnover was also enhanced by systemic administration of (-)-nicotine in various brain regions and its effect was blocked by MEC (Morgan and Pfeil 1979;Roth et al 1982;Kubo et al 1989). Therefore, (-)-nicotine stimulates the release and turnover of NA and DA.…”

Section: Introductionmentioning

confidence: 87%

Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

et al. 1997

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“…The physostigmine induced hypertensive reaction in the rat (Varagic, 1955;Varagic and Krstic, 1966) has been suggested to be mediated via increased sympathetic outflow of central origin (Mrsulja et al, 1968) requiring intact central adrenergic neurons (Kazic, 1973). Recently, nicotine has been reported to enhance the turnover of NA in the rat brain (Morgan and Pfeil, 1979). Recently, nicotine has been reported to enhance the turnover of NA in the rat brain (Morgan and Pfeil, 1979).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological analysis of a cholinergic receptor mediated regulation of brain norepinephrine neurons

Engberg

Svensson

1980

J. Neural Transmission

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The significance of the cholinergic receptors within the noradrenergic nucleus locus coeruleus (LC) was analyzed by using single unit recording techniques and microiontophoretic drug application of various cholinergic and anticholinergic drugs. Physostigmine (25--50 micrograms/kg), intravenously administered, caused increased firing of LC neurons and this effect was blocked by scopolamine but not by methylscopolamine. Also nicotine (10--50 micrograms/kg i.v.) caused activation of LC neurons, an effect which was antagonized by the presumed nicotinic antagonist mecamylamine (8 mg/kg) as well as scopolamine (0.5 mg/kg i.v.). The cholinergic receptor within the LC showed specific muscarinic characteristics since microiontophoretic application of various muscarinic agonists caused excitation of LC units, whereas microiontophoretically applied nicotine had no effect. In addition, the acetylcholine (ACh)-induced excitation of the LC neurons was not blocked by nicotinic antagonists but was totally antagonized by the muscarinic agonist scopolamine. Scopolamine, when microiontophoretically applied onto the LC neurons, antagonized the stimulatory effect of systemically injected physostigmine but not that of nicotine. These results suggest that the stimulation of noradrenaline (NA) neurons in the LC by cholinergic drugs such as physostigmine is mediated via cholinergic, muscarinic receptors within this nucleus. The LC activation by nicotine is, however, an indirect effect, probably involving central ACh release and mediated via a non-cholinergic LC input.

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“…Blockade of muscarinic receptors with atro pine and scopolamine considerably inhibited carbachol-induced WDS while nicotine an tagonist, mecamylamine [Morgan and Pfeil, 1979] failed to affect this behavior, which may suggest that WDS are mediated through the stimulation of muscarinic receptors. It should be underlined that scopolamine methyl nitrate, a peripherally active musca rinic antagonist, was ultimately ineffective against WDS produced by carbachol.…”

Section: Discussionmentioning

confidence: 94%

Studies on the Mechanism of Wet Dog Shakes Produced by Carbachol in Rats

Turski¹,

Czuczwar²,

Turski³

et al. 1984

Pharmacology

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In an attempt to elucidate the mechanism of wet dog shakes (WDS) produced by carbachol administered into the rat lateral brain ventricle, the effects of blockade of muscarinic and nicotinic receptors on shaking response and the effects of carbachol on central catecholaminergic, serotonergic (5-HT) and GABAergic functions were studied in rats. The muscarinic receptor antagonists, atropine and scopolamine attenuated WDS produced by carbachol, whilst a peripherally active muscarinic receptor antagonist, scopolamine methyl nitrate, failed to influence WDS. The nicotine antagonist, mecamylamine, did not affect WDS caused by carbachol either.

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Mecamylamine blockade of nicotine enhanced noradrenaline turnover in rat brain

Cited by 29 publications

References 6 publications

Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

Pharmacological analysis of a cholinergic receptor mediated regulation of brain norepinephrine neurons

Studies on the Mechanism of Wet Dog Shakes Produced by Carbachol in Rats

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