Nicotinic acetylcholine receptors as targets for antidepressants

Shytle, R. Douglas; Silver, Archie A.; Lukas, Ronald J.; Newman, Mary B.; Sheehan, David V.; Sanberg, Paul R.

doi:10.1038/sj.mp.4001035

Cited by 259 publications

(228 citation statements)

References 121 publications

(130 reference statements)

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“…These pentamers could be joined as α4 (2) β2 (3), α4 (3) β2 (2) , or homomeric α7 receptors. nAChR α6 subunits are not widely expressed in the brain, but are prevalent in midbrain DAergic regions associated with pleasure, reward, and mood control [15] , suggesting that α6*-nAChRs play critical roles in nicotine dependence and in the ability to modulate mood and emotion attributed to nicotine [16] .…”

Section: Impact Of Nachrs In Etoh Reward and Dependencementioning

confidence: 99%

Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence

Gao

Taylor

2014

Acta Pharmacol Sin

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Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH's effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol's abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.

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Section: Impact Of Nachrs In Etoh Reward and Dependencementioning

confidence: 99%

Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence

Gao

Taylor

2014

Acta Pharmacol Sin

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“…9 Potential indications currently under investigation include treatment of cocaine 10 and ethanol abuse, 11 to facilitate smoking cessation, [12][13][14][15] and to treat various neuropsychiatric disorders including anxiety, 16 epilepsy, 17,18 Tourette's disorder, 19 bipolar disorder 20 and major depression. 21,22 Mecamylamine also appears to be well suited for the prophylactic treatment of autonomic dysreflexia. 23,24 The purpose of this paper is to critically review the research available regarding the possible use of mecamylamine as an aid to smoking cessation and to propose testable hypotheses that could be studied in recalcitrant smokers with mild to moderate hypertension.…”

Section: Journal Of Human Hypertensionmentioning

confidence: 99%

Mecamylamine (Inversine®): an old antihypertensive with new research directions

et al. 2002

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Mecamylamine (Inversine  ), the first orally available antihypertensive agent, is now rarely used. Although celebrated in the 1950s, mecamylamine fell out of favour because of its widespread ganglionic side effects at antihypertensive doses (30-90 mg/day). However, recent studies suggest that mecamylamine is very effective at relatively low doses (2.5-5 mg b.i.d.) for blocking the physiological effects of nicotine and improving abstinence rates in smoking cessation studies, particularly for women. When these lower doses of mecamylamine are given, patients do not experience the severity of side effects that made the drug unpopular for the

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“…In the author's preliminary studies, NC-induced depression-like behavioral alterations in mice were reduced by some antidepressants, which have been used to treat major depression and to antagonize brain nicotinic acetylcholine receptors (nAChRs), the direct targets of NC [10,17,18]. The effects of such antidepressants have recently been characterized by their ability to cause neurogenesis in the hippocampus [19,20].…”

Section: Introductionmentioning

confidence: 99%

Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors

Hayase

2011

BMC Pharmacol

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BackgroundThe contributions of brain cannabinoid (CB) receptors, typically CB1 (CB type 1) receptors, to the behavioral effects of nicotine (NC) have been reported to involve brain transient receptor potential vanilloid 1 (TRPV1) receptors, and the activation of candidate endogenous TRPV1 ligands is expected to be therapeutically effective. In the present study, the effects of TRPV1 ligands with or without affinity for CB1 receptors were examined on NC-induced depression-like behavioral alterations in a mouse model in order to elucidate the "antidepressant-like" contributions of TRPV1 receptors against the NC-induced "depression" observed in various types of tobacco abuse.ResultsRepeated subcutaneous NC treatments (NC group: 0.3 mg/kg, 4 days), like repeated immobilization stress (IM) (IM group: 10 min, 4 days), caused depression-like behavioral alterations in both the forced swimming (reduced swimming behaviors) and the tail suspension (increased immobility times) tests, at the 2 h time point after the last treatment. In both NC and IM groups, the TRPV1 agonists capsaicin (CP) and olvanil (OL) administered intraperitoneally provided significant antidepressant-like attenuation against these behavioral alterations, whereas the TRPV1 antagonist capsazepine (CZ) did not attenuate any depression-like behaviors. Furthermore, the endogenous TRPV1-agonistic CB1 agonists anandamide (AEA) and N-arachidonyldopamine (NADA) did not have any antidepressant-like effects. Nevertheless, a synthetic "hybrid" agonist of CB1 and TRPV1 receptors, arvanil (AR), caused significant antidepressant-like effects. The antidepressant-like effects of CP and OL were antagonized by the TRPV1 antagonist CZ. However, the antidepressant-like effects of AR were not antagonized by either CZ or the CB1 antagonist AM 251 (AM).ConclusionsThe antidepressant-like effects of TRPV1 agonists shown in the present study suggest a characteristic involvement of TRPV1 receptors in NC-induced depression-like behaviors, similar to those caused by IM. The strong antidepressant-like effects of the potent TRPV1 plus CB1 agonist AR, which has been reported to cause part of its TRPV1-mimetic and cannabimimetic effects presumably via non-TRPV1 or non-CB1 mechanisms support a contribution from other sites of action which may play a therapeutically important role in the treatment of NC abuse.

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Nicotinic acetylcholine receptors as targets for antidepressants

Cited by 259 publications

References 121 publications

Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence

Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence

Mecamylamine (Inversine®): an old antihypertensive with new research directions

Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors

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