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Experimental and Clinical... Jun 2014Preclinical drug discrimination procedures have been useful in understanding the pharmacological mechanisms of the subjective-like effects of abused drugs. Converging...
Preclinical drug discrimination procedures have been useful in understanding the pharmacological mechanisms of the subjective-like effects of abused drugs. Converging lines of evidence from neurochemical and behavioral studies implicate a potential role of nicotinic acetylcholine (nACh) receptors in the abuse-related effects of cocaine. The aim of the present study was to determine the effects of the nACh receptor antagonist mecamylamine on the discriminative stimulus effects of cocaine in nonhuman primates. The effects of mecamylamine on the cocaine-like discriminative stimulus effects of nicotine were also examined. Male rhesus monkeys (n = 5) were trained to discriminate 0.32 mg/kg, IM cocaine from saline in a 2-key, food-reinforced discrimination procedure. Initially, potency and time course of cocaine-like discriminative stimulus effects were determined for nicotine and mecamylamine alone. Test sessions were then conducted examining the effects of mecamylamine on cocaine or the cocaine-like discriminative stimulus effects of nicotine. Curiously, mecamylamine produced partial cocaine-like discriminative stimulus effects. Mecamylamine did not significantly alter the discriminative stimulus effects of cocaine up to doses that significantly decreased rates of operant responding. Mecamylamine and nicotine combinations were not different than saline. These results confirm previous nonhuman primate studies of partial substitution with nicotine and extend these findings with mecamylamine. Furthermore, these results extend previous results in rats suggesting cocaine may have nACh receptor antagonist properties.
Topics: Animals; Cocaine; Discrimination Learning; Dose-Response Relationship, Drug; Macaca mulatta; Male; Mecamylamine; Nicotinic Antagonists; Receptors, Nicotinic
PubMed: 24548245
DOI: 10.1037/a0035274 -
Journal of Psychopharmacology (Oxford,... Feb 2012Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during...
Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during abstinence when exposure to any stressor ensues. However, the role of nicotinic acetylcholine receptors in the ethanol- and stress-induced reinstatement of ethanol-induced conditioned place preference has not yet been explored. Therefore, the present study investigated the influence of mecamylamine, a nicotinic acetylcholine receptors antagonist on acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in adult male Swiss mice. The results revealed that mecamylamine (0.1-10 µg/mouse, intracerebroventricularly) dose dependently prevented the development, expression, and reinstatement of ethanol-induced conditioned place preference. Further, acute treatment with mecamylamine blocked the restraint stress and forced swim stress-induced reinstatement of ethanol-induced conditioned place preference. All of these treatments had no influence on the locomotor activity. Therefore, it is concluded that mecamylamine blocks the acquisition, expression and reinstatement of conditioned reinforcing effects of ethanol without per se reinforcing or aversive influence. This ability of mecamylamine might be a potential advantage in the treatment of alcoholism.
Topics: Alcoholism; Animals; Conditioning, Psychological; Ethanol; Male; Mecamylamine; Mice; Motor Activity; Nicotinic Antagonists; Receptors, Nicotinic; Stress, Psychological
PubMed: 22182742
DOI: 10.1177/0269881111431749 -
Pharmacology, Biochemistry, and Behavior Sep 2011Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve... (Comparative Study)
Comparative Study
Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve memory function in dementia and reverse acetylcholine esterase (AChE) activity. The aim of this study was to investigate the effect of resveratrol on emotional and spatial memory in naive rats, as well as on scopolamine- and mecamylamine-induced memory impairment in the passive avoidance and Morris water maze (MWM) tests. Resveratrol (12.5, 25 and 50 mg/kg), scopolamine (0.6 mg/kg) and mecamylamine (10mg/kg) were administered to male Wistar rats. In the passive avoidance test, there was no significant difference in the first day latency between all groups, whereas scopolamine and mecamylamine significantly shortened the second day latency compared to the control group. Resveratrol reversed the effect of scopolamine at all doses used, but it had no effect on mecamylamine-induced memory impairment in the passive avoidance test. Both scopolamine and mecamylamine significantly decreased the time spent in the escape platform quadrant during the probe trial of the MWM test compared to the control group. Resveratrol reversed the effect of scopolamine at all doses, but did not change the effect of mecamylamine in the MWM test. There were no significant differences in the locomotor activities of any of the groups. In conclusion, we suggested that resveratrol had improving effects on learning and memory by acting on muscarinic cholinergic receptors and at least in part, may reverse AChE activity.
Topics: Animals; Avoidance Learning; Male; Maze Learning; Mecamylamine; Memory Disorders; Rats; Rats, Wistar; Reaction Time; Resveratrol; Scopolamine; Stilbenes
PubMed: 21624386
DOI: 10.1016/j.pbb.2011.05.017 -
Recent Patents on CNS Drug Discovery Aug 2012Alcohol dependence and other alcohol use disorders are major public health problems. Due to the limitations in efficacy with current medications for the management of... (Review)
Review
Alcohol dependence and other alcohol use disorders are major public health problems. Due to the limitations in efficacy with current medications for the management of alcohol abuse and dependence, there is a need for alterantive pharmacotherapies. Emerging preclinical and clinical data indicate that brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of ion channels expressed in the mammalian brain, are critical targets for the development of pharmacotherapies for alcohol abuse and dependence. Evidence suggests that the effects of nAChR partial agonists and antagonists have promise for the management of alcohol dependence and other alcohol use disorders. The present review summarizes information on the most recent pharmacotherapies targeting nAChRs, including cytisine, sazetidine A, varenicline, lobeline mecamylamine, PF-4575180 and CP-601932, that are able to treat alcohol dependence. The role of α4β2*, α3β4* and/or other subtypes associated effects in reducing voluntary alcohol consumption or modulate alcohol drinking behavior in animal models and humans are reviewed. Patents discussed include those targeting α4β2* and α7 subtypes as well as cholinesterase inhibitors. Future research indicating the ability of nAChR based compounds to reduce alcohol consumption or modulate alcohol drinking behavior in preclinical and clinical studies, are also discussed.
Topics: Alcohol Deterrents; Alcoholism; Animals; Disease Models, Animal; Humans; Mecamylamine; Molecular Targeted Therapy; Nicotinic Antagonists; Patents as Topic
PubMed: 22574675
DOI: 10.2174/157488912800673173 -
Lancet (London, England) Apr 1957
Topics: Autonomic Agents; Hypertension; Ileus; Intestinal Obstruction; Mecamylamine
PubMed: 13417574
DOI: 10.1016/s0140-6736(57)91170-4 -
Pharmacology, Biochemistry, and Behavior Jun 1990The nicotinic antagonist mecamylamine (2.5 and 5 mg/kg/IP) depressed both active (shuttle-box) and passive (step-through) avoidance learning in mice of the DBA/2 strain....
The nicotinic antagonist mecamylamine (2.5 and 5 mg/kg/IP) depressed both active (shuttle-box) and passive (step-through) avoidance learning in mice of the DBA/2 strain. The nootropic drug oxiracetam (50 and 100 mg/kg/IP) improved acquisition in the multitrial active avoidance test, but had no effect on one-trial passive avoidance learning. When the two drugs were combined, oxiracetam did not counteract mecamylamine-induced impairment of passive avoidance learning, even if it maintained a facilitating action on shuttle-box avoidance acquisition in mice receiving the nicotinic receptor blocker. Prevention of mecamylamine-induced shuttle-box avoidance depression by oxiracetam indicates that central nicotinic mechanisms are probably involved in the improving effects exerted by nootropic drugs on learning.
Topics: Animals; Avoidance Learning; Drug Interactions; Electric Stimulation; Male; Mecamylamine; Mice; Mice, Inbred DBA; Motor Activity; Nicotinic Antagonists; Pain; Psychotropic Drugs; Pyrrolidines; Sensory Thresholds
PubMed: 2356212
DOI: 10.1016/0091-3057(90)90420-m -
The Journal of Pharmacology and... Nov 1966
Topics: Animals; Avoidance Learning; Behavior, Animal; Learning; Mecamylamine; Mice; Nicotine; Quaternary Ammonium Compounds
PubMed: 5950956
DOI: No ID Found -
British Journal of Pharmacology Jun 2018Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse...
BACKGROUND AND PURPOSE
Evidence suggests that exercise decreases nicotine withdrawal symptoms in humans; however, the mechanisms mediating this effect are unclear. We investigated, in a mouse model, the effect of exercise intensity during chronic nicotine exposure on nicotine withdrawal severity, binding of α4β2*, α7 nicotinic acetylcholine (nAChR), μ-opioid (μ receptors) and D dopamine receptors and on brain-derived neurotrophic factor (BDNF) and plasma corticosterone levels.
EXPERIMENTAL APPROACH
Male C57Bl/6J mice treated with nicotine (minipump, 24 mg·kg ·day ) or saline for 14 days underwent one of three concurrent exercise regimes: 24, 2 or 0 h·day voluntary wheel running. Mecamylamine-precipitated withdrawal symptoms were assessed on day 14. Quantitative autoradiography of α4β2*, α7 nAChRs, μ receptors and D receptor binding was performed in brain sections of these mice. Plasma corticosterone and brain BDNF levels were also measured.
KEY RESULTS
Nicotine-treated mice undertaking 2 or 24 h·day wheel running displayed a significant reduction in withdrawal symptom severity compared with the sedentary group. Wheel running induced a significant up-regulation of α7 nAChR binding in the CA2/3 area of the hippocampus of nicotine-treated mice. Neither exercise nor nicotine treatment affected μ or D receptor binding or BDNF levels. Nicotine withdrawal increased plasma corticosterone levels and α4β2* nAChR binding, irrespective of exercise regimen.
CONCLUSIONS AND IMPLICATIONS
We demonstrated for the first time a profound effect of exercise on α7 nAChRs in nicotine-dependent animals, irrespective of exercise intensity. These findings shed light onto the mechanism underlining the protective effect of exercise on the development of nicotine dependence.
LINKED ARTICLES
This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.
Topics: Animals; Male; Mecamylamine; Mice; Mice, Inbred C57BL; Nicotine; Protective Agents; Up-Regulation; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 29266170
DOI: 10.1111/bph.14068 -
British Journal of Diseases of the Chest Oct 1961
Topics: Autonomic Agents; Autonomic Nervous System; Chlorothiazide; Hypertension; Mecamylamine; Outpatients
PubMed: 13871970
DOI: 10.1016/s0007-0971(61)80066-1 -
Depression and Anxiety 2002
Clinical Trial Randomized Controlled Trial
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Mecamylamine; Neurons; Nicotinic Antagonists; Receptors, Nicotinic; Tourette Syndrome
PubMed: 12415531
DOI: 10.1002/da.10035