Evidence for modulation of GABAergic neurotransmission by nicotine

Freun, Ronald K.; Jungschaffer, Dana A.; Collins, Allan C.; Wehner, Jeanne M.

doi:10.1016/0006-8993(88)90160-6

Cited by 48 publications

(16 citation statements)

References 26 publications

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“…Freund et al (1988), Chiodini et al (1999), and Alkondon et al (2000) speculated that seizures induced by high doses of nicotine are the result of a decrease in GABAergic function. In this model, nicotinic cholinergic fibers provide excitatory input to GABAergic neurons, which in turn inhibit excitatory pyramidal cells.…”

Section: Discussionmentioning

confidence: 99%

“…Blockade of the nicotinic cholinergic input to GABAergic neurons (either by desensitization or antagonism) reduces GABAergic input to pyramidal cells, resulting in increased excitability and seizures. Freund et al (1988) showed that bath application of high concentrations of nicotine induced epileptiform activity in CA1 pyramidal cells in mouse hippocampal slices. This effect was similar to that produced by bath application of bicuculline and was blocked by bath application of GABA or compounds that increase GABAergic function.…”

Section: Discussionmentioning

confidence: 99%

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GABAergic Systems Modulate Nicotinic Receptor-Mediated Seizures in Mice

Dobelis

Hutton²,

Lu³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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The pharmacology of nicotinic receptor-mediated seizures was investigated in C3H mice. Eleven nicotinic agonists and six antagonists were administered centrally (i.c.v.). Epibatidine and epiboxidine were the most potent agonists tested, whereas acetylcholine and the ␣7*-selective compounds 3-(2,4-dimethoxybenzylidene)-anabaseine (GTS-21) and anabasine, were the least potent. Nicotine-induced seizures were blocked by cotreatment with either the nonselective antagonist mecamylamine or the ␣7*-selective antagonist methyllycaconitine. The ␣4␤2*-selective antagonist dihydro-␤-erythroidine was ineffective at blocking seizures. However, high doses of all six antagonists tested were fully efficacious in producing seizures, with d-tubocurarine being the most potent and mecamylamine the least potent. Potential relationships between nicotinic receptor-mediated seizures and drug effects on GABA function were also investigated. No correlation was seen between potencies of the agonists in producing seizures and We also compared inbred mouse strain sensitivity to nicotine, picrotoxin, bicuculline, and kainate-induced seizures. Robust positive correlations were revealed for nicotine-induced seizures and seizures induced by either picrotoxin or bicuculline, both GABA A receptor antagonists. No correlation was found between nicotineinduced seizures and those induced by the excitatory amino acid receptor agonist kainate. Based on these findings, we present a model for nicotinic receptor-mediated seizures mediated through GABAergic systems.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GABAergic Systems Modulate Nicotinic Receptor-Mediated Seizures in Mice

Dobelis

Hutton²,

Lu³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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“…This derangement of the ERK MAPK signaling cascade may underlie the learning and memory deficits attributed to hippocampal dysfunction in AD. An additional site of action is likely to be disruption of the normal function of the hippocampal circuit, specifically the altered excitability of pyramidal neurons because ␣7 nAChRs located on GABAergic interneurons can regulate hippocampal pyramidal neuron excitability (Freund et al, 1988(Freund et al, , 1990Frazier et al, 1998). Modifications of GABAergic signaling to area CA1 pyramidal neurons in the hippocampi of animals in which A␤ production is either enhanced or genetically knocked-out have been demonstrated (Fitzjohn et al, 2000;Zaman et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease

et al. 2001

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Alzheimer's Disease (AD) is the most common of the senile dementias, the prevalence of which is increasing rapidly, with a projected 14 million affected worldwide by 2025. The signal transduction mechanisms that underlie the learning and memory derangements in AD are poorly understood. ␤-Amyloid (A␤) peptides are elevated in brain tissue of AD patients and are the principal component of amyloid plaques, a major criterion for postmortem diagnosis of the disease. Using acute and organotypic hippocampal slice preparations, we demonstrate that A␤ peptide 1-42 (A␤42) couples to the mitogen-activated protein kinase (MAPK) cascade via ␣7 nicotinic acetylcholine receptors (nAChRs). In vivo elevation of A␤, such as that exhibited in an animal model for AD, leads to the upregulation of ␣7 nAChR protein. ␣7 nAChR upregulation occurs concomitantly with the downregulation of the 42 kDa isoform of extracellular signal-regulated kinase (ERK2) MAPK in hippocampi of aged animals. The phosphorylation state of a transcriptional mediator of long-term potentiation and a downstream target of the ERK MAPK cascade, the cAMP-regulatory element binding (CREB) protein, were affected also. These findings support the model that derangement of hippocampus signal transduction cascades in AD arises as a consequence of increased A␤ burden and chronic activation of the ERK MAPK cascade in an ␣7 nAChR-dependent manner that eventually leads to the downregulation of ERK2 MAPK and decreased phosphorylation of CREB protein.

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“…Nicotine appears to have effects in disrupting GABAergic transmission in the hippocampus. However, it does not alter binding of GABA or benzodiazepine ligands (Freund et al 1988). GABA antagonist bicuculline has been shown to block nicotinic receptors (Zhang and Feltz 1991).…”

Section: Other Transmitter Systemsmentioning

confidence: 98%

Nicotinic systems and cognitive function

1992

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Nicotinic acetylcholine receptors have been found to be important for maintaining optimal performance on a variety of cognitive tasks. In humans, nicotine-induced improvement of rapid information processing is particularly well documented. In experimental animals nicotine has been found to improve learning and memory on a variety of tasks, while the nicotinic antagonist mecamylamine has been found to impair memory performance. Nicotine has been found to be effective in attenuating memory deficits resulting from lesions of the septohippocampal pathway or aging in experimental animals. Nicotinic receptors are decreased in the cortex of patients with Alzheimer's disease. Preliminary studies have found that some aspects of the cognitive deficit in Alzheimer's disease can be attenuated by nicotine. Nicotine may prove to be useful therapeutic treatment for this and other types of dementia.

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Evidence for modulation of GABAergic neurotransmission by nicotine

Cited by 48 publications

References 26 publications

GABAergic Systems Modulate Nicotinic Receptor-Mediated Seizures in Mice

GABAergic Systems Modulate Nicotinic Receptor-Mediated Seizures in Mice

β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease

Nicotinic systems and cognitive function

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