A Nicotine Antagonist, Mecamylamine, Reduces Cue-Induced Cocaine Craving in Cocaine-Dependent Subjects

Reid, Malcolm S.; Mickalian, Joanne D.; Delucchi, Kevin; Berger, Stanley A.

doi:10.1016/s0893-133x(98)00076-1

Cited by 123 publications

(89 citation statements)

References 21 publications

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“…If the reinforcement-enhancing effect of nicotine impacts a range of salient nonpharmacological stimuli, then it could also enhance the ability of environmental stimuli conditioned to other drugs to elicit craving and drug seeking. In support of this hypothesis, nicotine has been shown to augment cocaine craving produced by cocaine-related cues (Reid et al 1999), and this effect is reduced by the nicotinic receptor antagonist, mecamylamine (Reid et al 1999). Smoking cues can also stimulate craving for alcohol (Palfai et al 2000).…”

Section: Discussionmentioning

confidence: 93%

“…An important consequence of these effects is that the reinforcement-enhancing properties of nicotine could also impact the behavioral effects of environmental stimuli that become conditioned reinforcers for other co-abused drugs, such as alcohol and cocaine. In support of this theory, Reid and colleagues (Reid et al 1998) demonstrated that cue-induced cocaine craving was augmented by nicotine, and that the nicotinic receptor antagonist mecamylamine reduced this effect (Reid et al 1999). Along similar lines, alcohol cues induce craving for tobacco smoking in subjects who abuse both drugs (Gulliver et al 1995;Rohsenow et al 1997;Drobes 2002), and smoking cues also elicit craving for alcohol (Palfai et al 2000).…”

Section: Implications For Smokingmentioning

confidence: 94%

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Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

et al. 2005

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Although considerable progress has been made we do not yet fully understand the behavioral and neurobiological bases of nicotine reinforcement, and without this knowledge treatment strategies aimed at reducing smoking remain deficient. This dissertation provides an original perspective on nicotine reinforcement, which arises from substantial evidence of complex interactions between nicotine and nonpharmacological stimuli. The present experiments tested the hypothesis that nicotine reinforcement derives from at least two sources: 1) the primary reinforcing properties of nicotine, an action that requires response-dependent drug administration, and 2) the more prominent ability of nicotine to enhance behavior maintained by salient non-nicotine stimuli, an action that does not require a contingent relationship between drug administration and reinforced operant responding. Although novel for nicotine, this hypothesis has origins in an extensive literature on the reinforcing properties of psychostimulant drugs. Empirical support for the application of this hypothesis to nicotine reinforcement will be presented. By investigating the interaction between nicotine and nonpharmacological stimuli within the context of drug selfadministration in rats, the present research has generated new insights into the paradox of how nicotine, an apparently weak primary reinforcer, can sustain the robust behavior observed in selfadministration and in smoking. Hypotheses generated by these data provide important direction for future investigations into the neurobiology of nicotine reinforcement.iii

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Section: Discussionmentioning

confidence: 93%

Section: Implications For Smokingmentioning

confidence: 94%

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

et al. 2005

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“…In contrast, a clinical laboratory study revealed that the nicotinic receptor antagonist mecamylamine decreased craving in cocaine-dependent subjects (Reid et al, 1999), although its effectiveness in relapse prevention is unknown. This mirrors preclinical work demonstrating that mecamylamine suppressed both nicotine and cocaine self-administration (Blokhina et al, 2005).…”

Section: Summary and Future Directions For Clinical Researchmentioning

confidence: 96%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

164

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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“…8 The principal focus of research on other clinical indications largely involves mecamylamine's potent blockade of brain nicotinic receptors at doses that do not have a significant effect on parasympathetic function (2.5-10 mg/day). 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.…”

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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A Nicotine Antagonist, Mecamylamine, Reduces Cue-Induced Cocaine Craving in Cocaine-Dependent Subjects

Cited by 123 publications

References 21 publications

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

The Role of Acetylcholine in Cocaine Addiction

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

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