Nicotine effects in mouse hippocampus are blocked by mecamylamine, but not other nicotinic antagonists

Freund, Ronald K.; Jungschaffer, Dana A.; Collins, Allan C.

doi:10.1016/0006-8993(90)90160-d

Cited by 25 publications

(8 citation statements)

References 34 publications

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“…The improvement in sensory inhibition was accomplished primarily through a decrease in the amplitude of response to the test stimulus, with less change in response to the conditioning stimulus, again, similar to nicotine (Stevens and Wear 1997). Apparent mediation of the GTS-21-induced improvement in sensory inhibition through the a 7 nicotinic receptor was demonstrated by blockade of the improvement with central administration of the selective antagonist for the a 7 receptor, a-bungarotoxin (Couturier et al 1990), but not the very selective neuronal (a 4 b 2 ) nicotinic channel blocker, mecamylamine (Williams and Robinson 1984;Freund et al 1990). This is similar to the e¤ects observed with co-administration of either a-bungarotoxin or mecamylamine and ABT418, a mixed a 7 and a 4 b 2 agonist (Stevens and Wear 1997).…”

Section: Discussionmentioning

confidence: 83%

Selective α 7 -nicotinic agonists normalize inhibition of auditory response in DBA mice

et al. 1998

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Abnormal sensory inhibition is a measurable indicator of a sensory processing deficit which is observed in schizophrenia, and other disorders, and which may be heritable. This deficit has also been observed in certain inbred mouse strains where the intensity of the deficit has been correlated with reduction in the number of hippocampal alpha-bungarotoxin-sensitive nicotinic receptors. Nicotine and certain nicotinic agonists produce brief periods of normal sensory inhibition in these mice. Similarly, nicotine also transiently normalizes sensory inhibition in schizophrenics. The present study assessed the effects of a novel nicotinic partial agonist (GTS-21), selective for the alpha-bungarotoxin site, on sensory inhibition in DBA mice, a strain with no sensory inhibition under routine experimental conditions. GTS-21 produced a dose-dependent normalization of sensory inhibition which was blocked by alpha-bungarotoxin but not mecamylamine. In contrast to other nicotinic agonists, normalization of sensory inhibition by GTS-21 and two related anabaseine compounds, DMAB-anabaseine and DMAC-anabaseine, was observed when administered a second time to the animal, after a 40-min delay. Our results indicated that the anabaseine compounds increase sensory inhibition through alpha7 nicotinic receptors, and that their ability to act repeatedly on these receptors may be less affected by desensitization.

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Section: Discussionmentioning

confidence: 83%

Selective α 7 -nicotinic agonists normalize inhibition of auditory response in DBA mice

et al. 1998

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“…CA3 is the area where physiological effects sensitive to cu-BT have been reported (Miner and Collins, 1989;Luntz-Leybman et al, 1992). By contrast, electrophysiological effects of nicotine in CA1 are not blocked by a-BT (Freund et al, 1990). It is possible that the coexistence of (~3 subunits in some CA1 cells may obscure the effects of a-BT-sensitive receptors, as in the singlecell expression systems described above.…”

Section: Discussionmentioning

confidence: 90%

Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression

et al. 1993

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The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA- containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.

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“…For example, Freund et al [1990] reported that two nicotinic antagonists, d-tubocurarine and α-bungarotoxin, produced excitatory effects (i.e., increased population spikes in mouse hippocampal slices) that were quantitatively similar to those of nicotine. Mec, d-tubocurarine and α-bungarotoxin (at relatively high concentrations) released iontophoretically into the hippocampus (CA1 region) of anesthetized rats produced excitation (increased population spikes) rather than inhibition of electrical discharges [Ropert and Krnjevic, 1982].…”

Section: Response Latenciesmentioning

confidence: 94%

“…Intrahypothalamic injection of d-tubocurarine has produced excitatory behavioral responses (i.e., fear and escape reactions) in rats [Decsi and Karmos-Varszegi, 1969;Buccafusco and Brezenoff, 1980] in a similar fashion to carbachol. In reference to the underlying physiological basis for these observations, Freund et al [1990] suggested that the excitatory effects of nicotine, d-tubocurarine, and α-bungarotoxin might be a consequence of diminished GABAergic transmission (i.e., nicotine through desensitization of the nAChR, which controls GABA release, and the later agents by direct antagonism. The excitatory effects on mouse hippocampal slices (in their study) were not observed with mec and, in fact, mec inhibited population spikes.…”

Section: Response Latenciesmentioning

confidence: 96%

Dose‐specific improvements in memory‐related task performance by rats and aged monkeys administered the nicotinic‐cholinergic antagonist mecamylamine

Terry

Buccafusco

Prendergast

1999

Drug Development Research

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Nicotine effects in mouse hippocampus are blocked by mecamylamine, but not other nicotinic antagonists

Cited by 25 publications

References 34 publications

Selective α 7 -nicotinic agonists normalize inhibition of auditory response in DBA mice

Selective α 7 -nicotinic agonists normalize inhibition of auditory response in DBA mice

Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression

Dose‐specific improvements in memory‐related task performance by rats and aged monkeys administered the nicotinic‐cholinergic antagonist mecamylamine

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