Effects of Galantamine, a Nicotinic Allosteric Potentiating Ligand, on Nicotine-Induced Catecholamine Release in Hippocampus and Nucleus Accumbens of Rats

Sharp, Burt M.; Yatsula, Mike; Fu, Yongjian

doi:10.1124/jpet.103.063586

Cited by 24 publications

(14 citation statements)

References 38 publications

(45 reference statements)

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“…An in vivo microdialysis study showed that galantamine with nicotine at ineffective doses increased noradrenaline release, although galantamine (3 mg/kg) alone did not affect the release in the hippocampus of rats (33). This study also demonstrated that galantamine enhanced nicotine-stimulated noradrenaline release.…”

Section: Noradrenalinesupporting

confidence: 61%

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

et al. 2011

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Abstract. Several lines of evidence suggest that cholinergic deficits may contribute to the pathophysiology of psychiatric disorders as well as Alzheimer's disease. There is growing clinical evidence that galantamine, currently used for the treatment of Alzheimer's disease, may improve cognitive dysfunction and psychiatric illness in schizophrenia, major depression, bipolar disorder, and alcohol abuse. Since galantamine is a rather weak acetylcholinesterase inhibitor, but has additional allosteric potentiating effects at nicotinic receptors, it affects not only cholinergic transmission but also other neurotransmitter systems such as monoamines, glutamate, and γ-aminobutyric acid (GABA) through its allosteric mechanism. It is likely that these effects may result in more beneficial effects. To understand the underlying mechanism for the clinical effectiveness of galantamine, neuropharmacological studies have been performed in animal models of several psychiatric disorders. These studies suggest that not only the nicotinic receptor-modulating properties but also the muscarinic receptor activation contribute to the antipsychotic effect and improvement of cognitive dysfunction by galantamine. This review summaries the current status on the pharmacology of galantamine, focusing on its effect on neurotransmitter release and pharmacological studies in animal models of psychiatric disorders.

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Section: Noradrenalinesupporting

confidence: 61%

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

et al. 2011

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“…Thus, it appears that galantamine enhances dopaminergic activity most effectively at a dose that results only in minor AChE inhibition (Geerts et al, 2005), and the effect may therefore rather be due to allosteric potentiation of nAChRs. In support of this conclusion, a recent study reported that a higher dose of galantamine (3.0 mg/kg s.c.) did not increase dopamine efflux in the nucleus accumbens (Sharp et al, 2004).…”

Section: Discussionmentioning

confidence: 66%

Galantamine Enhances Dopaminergic Neurotransmission In Vivo Via Allosteric Potentiation of Nicotinic Acetylcholine Receptors

Schilström

Ivanov

Wiker

et al. 2006

Neuropsychopharmacol

115

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Clinical studies suggest that adjunct galantamine may improve negative and cognitive symptoms in schizophrenia. These symptoms may be related to impaired dopaminergic function in the prefrontal cortex. Indeed, galantamine has been shown to increase dopamine release in vitro. Galantamine is an allosteric modulator of nicotinic acetylcholine receptors (nAChRs) and, at higher doses, an acetylcholine esterase (AChE) inhibitor. We have previously shown that nicotine, through stimulation of nAChRs in the ventral tegmental area (VTA), activates midbrain dopamine neurons and, hence, potentiation of these receptors could be an additional mechanism by which galantamine can activate dopaminergic pathways. Therefore, the effects of galantamine (0.01-1.0 mg/kg s.c.) on dopamine cell firing were tested in anaesthetized rats. Already at a low dose, unlikely to result in significant AchE inhibition, galantamine increased firing activity of dopaminergic cells in the VTA. The effect of galantamine was prevented by the nAChR antagonist mecamylamine (1.0 mg/kg s.c.), but not the muscarinic receptor antagonist scopolamine (0.1 mg/kg s.c.), and it was not mimicked by the selective AChE inhibitor donepezil (1.0 mg/kg s.c.). Our data thus indicate that galantamine increases dopaminergic activity through allosteric potentiation of nAChRs. Galantamine's effect was also prevented by the a7 nAChR antagonist methyllycaconitine (6.0 mg/kg i.p.) as well as the N-methyl-Daspartate antagonist CGP39551 (2.5 mg/kg s.c.), indicating a mechanism involving presynaptic facilitation of glutamate release. In parallel microdialysis experiments, galantamine was found to increase extracellular levels of dopamine in the medial prefrontal cortex. These results may have bearing on the enhancement of negative and cognitive symptoms in schizophrenia.

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“…Nicotine in vivo stimulated increases in hippocampal and accumbal NE and DA levels. Galantamine stimulated the NE but not the DA response, indicating that different circuits are involved in NE versus DA release, and that there are differences in the responses of cognitive versus reward areas (28). In cortical and hippocampal slices, nicotine-induced NE release was inhibited by cholinergic and glutamatergic antagonists, indicating the participation of acetylcholine receptors on glutamatergic neurons (29).…”

Section: Nicotine-induced Neurotransmitter Changes In Areas Involved mentioning

confidence: 98%

The Effects of Cholinergic and Dopaminergic Antagonists on Nicotine-Induced Cerebral Neurotransmitter Changes

et al. 2005

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In a continuing study of nicotine-induced mechanisms in brain areas associated with cognitive processes, the effects of cholinergic and dopaminergic antagonists on nicotine-induced changes in dopamine, norepinephrine, and serotonin were examined. These effects were measured via in vivo microdialysis in the dorsal and ventral hippocampus and in the prefrontal and medial temporal cortex of conscious, freely moving, adult male rats. Nicotine (0.3 mg/kg, free base) was administered subcutaneously and the antagonists were infused locally via the microdialysis probe. Nicotine alone induced an increase of dopamine and its metabolites in all areas, an increase of norepinephrine in the cortex, and an increase of the norepinephrine metabolite 4-hydroxy-3-methoxy-phenylglycol in all areas. Serotonin was decreased in the hippocampus and increased in the cortex. Nicotine-induced dopamine increases were inhibited by nicotinic (mecamylamine 100 microM, methyllycaconitine 500 microM), muscarinic (atropine 100 microM), and dopaminergic D1 (SCH23390 100 microM) and D2 (eticlopride 100 microM) antagonists, in the hippocampal and cortical areas. In the hippocampal areas, these antagonists had less significant effect on norepinephrine and serotonin. However, in the cortical areas, all antagonists inhibited the nicotine-induced increase of serotonin to varying degrees; and some, primarily nicotinic and dopamine D1 antagonists, inhibited the induced increase of norepinephrine. In the hippocampal and cortical areas, the mechanisms of nicotine-induced dopamine increase seem to be similar, but the mechanisms seem to be different for noradrenergic and serotonergic systems, as shown by the fact that nicotine induces no change in norepinephrine and a decrease in serotonin in the hippocampus, while it induces an increase in both in the cortex. Nicotine-induced dopamine release seems to be mediated, in part locally, by nicotinic and muscarinic receptors on dopaminergic cells. In contrast, nicotine's effect on norepinephrine and serotonin is at least partially mediated by initial changes at other than local sites, and through different receptors. Thus, the effects of nicotine and the mechanisms involved differ for different neurotransmitters and in different brain areas.

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Effects of Galantamine, a Nicotinic Allosteric Potentiating Ligand, on Nicotine-Induced Catecholamine Release in Hippocampus and Nucleus Accumbens of Rats

Cited by 24 publications

References 38 publications

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

Galantamine Enhances Dopaminergic Neurotransmission In Vivo Via Allosteric Potentiation of Nicotinic Acetylcholine Receptors

The Effects of Cholinergic and Dopaminergic Antagonists on Nicotine-Induced Cerebral Neurotransmitter Changes

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