GABAA receptor antagonists enhance cortical acetylcholine release induced by 5-HT3 receptor blockade in freely moving rats

Diez-Ariza, M.; García-Alloza, Mónica; Lasheras, B.; Rı́o, Joaquı́n Del; Ramı́rez, Marı́a J.

doi:10.1016/s0006-8993(02)03483-2

Cited by 33 publications

(14 citation statements)

References 29 publications

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“…No pharmacokinetic interaction between these compounds has been described and, therefore, such an interaction should not account for the effects on cognition of the combined treatments, although this mechanism cannot be completely discarded, as all of these drugs, in particular ondansetron, have a common hepatic metabolism through multiple forms of cytochrome P450 (Dixon et al 1995;Klotz 1988). On the other hand, the results of our previous microdialysis study (Díez-Ariza et al 2002) rather suggest that there is a potentiation and not a prolongation by flumazenil of the effect of ondansetron on extracellular ACh levels.…”

Section: Discussioncontrasting

confidence: 67%

Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats

et al. 2003

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Section: Discussioncontrasting

confidence: 67%

Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats

et al. 2003

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“…Interestingly, and at both 7 and 30 days after lesion, concomitant administration of ondansetron with flumazenil significantly increased ACh release (expressed as maximum release, cumulated release or AUC) even though single treatment with either drug was ineffective. As might be expected, the increase in ACh release after the combined treatment in lesioned animals was lower than in control animals (Diez-Ariza et al, 2002). However, it should be noted that the releasing effect of the combined treatment was similar to the effect of a high depolarizing stimulus, such as KCl (100 mM), known to produce a maximal ACh release both in young or aged rats (Herzog et al, 2003) or after a cholinergic lesion (Rosenblad and Nilsson, 1993).…”

Section: Discussionmentioning

confidence: 53%

“…After collection of three baseline fractions, tested drugs were administered i.p. The doses of drugs used were selected according to previous experiments in non-lesioned animals (Diez-Ariza et al, 2002, 2003. In another set of experiments, animals were perfused with KCl (100 mM) through the dialysis probe.…”

Section: Acetylcholine Release ''In Vivo''mentioning

confidence: 99%

Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation

Gil-Bea

2004

Neuropharmacology

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We have studied the effects of concomitant blockade of 5-HT 3 and GABA A receptors on acetylcholine (ACh) release in the frontal cortex of rats with a selective cholinergic lesion. Lesions were performed by microinjection of the cholinergic toxin 192 IgG-saporin into the nucleus basalis magnocellularis. Single treatment with either the 5-HT 3 receptor antagonist ondansetron, 0.1 lg/kg, or the GABA A receptor benzodiazepine site antagonist flumazenil, 10 mg/kg, did not affect ACh release. However, the combined ondansetron þ flumazenil administration significantly increased ACh release to a similar extent as a depolarising stimulus with K + , 100 mM, at both 7 and 30 days post-lesion. Cortical perfusion with the combined ondansetron þ flumazenil treatment also increased [ 3 H]ACh efflux ''in vitro'' 30 days after lesion, suggesting that local events within the frontal cortex may participate in the interaction of ondansetron with GABAergic neurons, modulating ACh release in situations of cholinergic hypoactivity. No differences in the expression of 5-HT 3 and GABA A receptors in the frontal cortex were found after the cholinergic lesion. These results suggest that a combined ondansetron þ flumazenil treatment would contribute to restoring a diminished cholinergic function and may provide a basis for using this treatment in the therapy of cognitive disorders associated with degeneration of the cholinergic system. #

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“…In fact, GABA affects cholinergic neurotransmission at multiple central nervous system levels [66]. GABA A antagonists enhance the release of Ach at the level of the cerebral cortex in rats [66,67] and at the forebrain level in cats [68]. Vice versa, cortical interneurons containing GABA have nicotinic as well as muscarinic receptors and receive rich cholinergic afferents [69].…”

Section: Discussionmentioning

confidence: 99%

A Review of Transcranial Magnetic Stimulation in the in vivo Functional Evaluation of Central Cholinergic Circuits in Dementia

Nardone

Golaszewski²,

Ladurner³

et al. 2011

Dement Geriatr Cogn Disord

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Central cholinergic circuits of human brain can be tested non-invasively by coupling electrical peripheral stimulation with transcranial magnetic stimulation (TMS) of the motor cortex. The short-latency afferent inhibition (SAI) is reduced in cholinergic forms of dementia, such as Alzheimer disease (AD) and dementia with Lewy bodies, while it is normal in non-cholinergic forms of dementia, such as frontotemporal dementia. This finding suggests that this method can be used as a non-invasive additional tool for discriminating between cholinergic and non-cholinergic forms of dementia. Interestingly, SAI was also found to be significantly smaller in early AD patients. Identification of SAI abnormalities that occur early in the course of AD will allow earlier diagnosis and treatment with cholinergic drugs. In patients with vascular dementia, SAI responses varied widely; the number of patients with abnormal SAI conceivably reflects the percentage of subjects with a significant cholinergic dysfunction. It has recently been demonstrated that brain microbleeds have an impact on SAI that is independent of the extent of associated white matter changes and ischemic stroke. Since SAI can be increased by acetylcholinesterase inhibitors, TMS may help in identifying the patients who would be suitable for long-term treatment with cholinergic agents.

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GABAA receptor antagonists enhance cortical acetylcholine release induced by 5-HT3 receptor blockade in freely moving rats

Cited by 33 publications

References 29 publications

Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats

Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats

Facilitation of cholinergic transmission by combined treatment of ondansetron with flumazenil after cortical cholinergic deafferentation

A Review of Transcranial Magnetic Stimulation in the in vivo Functional Evaluation of Central Cholinergic Circuits in Dementia

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