Nicotine reinforcement

Like mAChRs, nAChRs have been implicated in the etiology of ALheimef s disease and related dementias as well as in gastrointestinal and cardiovascular disorders. Nicotine has high abuse potential and is the primary component in reinforcing smoking behaviors. Nicotine patches have been... 

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

Nicotine differs from cocaine in that it is powerfully reinforcing in the absence of subjective euphoria. The high incidence of cancerogenicity associated with longterm tobacco use is associated with compounds other than nicotine that are also contained in tobacco. Main... 

Caffeine and nicotine have more complex reinforcing effects on dopamine. Caffeine, a methylxanthine compound, appears to exert its central ac-... 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

In humans, a comparative examination of the positive reinforcing effects of solvents showed that among inhalant-dependent subjects, solvents induced a more intense sensation of pleasant feelings than that induced by alcohol and nicotine in subjects addicted to these substances (Kono et al. 2001). Solvent-dependent subjects reported pleasant feelings comparable to those reported by stimulant-dependent subjects after use of methamphetamine. However,... 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Oncken CA, Hatsukami DK, Lupo VR, et al Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther 59 654-61, 1996 Pomerleau OF, Pomerleau CS Neuroregulators and the reinforcement of smoking towards a biobehavioral explanation. Neurosci Biobehav Rev 8 503—513, 1984 Prochazka AV, Weaver MJ, Keller RT, et al A randomized trial of nortriptyline for smoking cessation. Arch Intern Med 158 2035-2039, 1998 Puska P, Korhonen HJ, Vartiainen E, et al Combined use of nicotine patch and gum compared with gum alone in smoking cessation a clinical trial in North Karelia. Tob Control 4 231-235, 1995... 

Changeux, JP, Bertrand, D, Corringer, PJ, Dehoene, S, Edelstein, S, Leno, C, Novere, N le, Marubio, L, Picciotto, M and Zoli, M (1998) Brain nicotinic receptors structure and regulation, role in learning and reinforcement. Brain Res. Rev. 26 198-216. 

Studies in knockout mice indicate that the p2 nAChRs are necessary for nicotine self-administration, DA-dependent locomotor activation, and nicotine-associated enhancement of NAc DA release.40-51 53 Combined with studies showing that antagonism of the high-affinity nAChRs block self-administration,44-54 it would appear that p2 nAChRs are particularly critical for nicotine reinforcement. Unlike wild-type mice that self-administer both cocaine and nicotine, p2 nAChR-null mutant mice learn to self-administer cocaine normally, but stop bar pressing as though receiving saline when cocaine is switched to nicotine.40 Self-administration of VTA nicotine and associated DA release is rescued, however, in p2 nAChR knockout mice with lentiviral-mediated expression of P2 subunit DNA in the VTA.55 Whereas several configurations of the p2 nAChRs exist at the... 

Not only do cues control nicotine use, but nicotine exposure also enhances conditioned reinforcement in rats and mice for weeks following exposure to nicotine106-109 (Figure 2.4), and can... 

Picciotto, M.R., Zoli, M., Rimondini, R. et al. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature. 391 173, 1998. 

Corrigall, W.A., Franklin, K.B., Coen, K.M., Clarke, P.B. The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology (Berlin). 107 285, 1992. 

Maskos, U., Molles, B.E., Pons, S. et al. Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature. 436 103, 2005. 

Perkins, K.A., Gerlach, D., Vender, J., Grobe, J., Meeker, J., Hutchison, S. Sex differences in the subjective and reinforcing effects of visual and olfactory cigarette smoke stimuli. Nicotine Tob. Res. 3 141, 2001. 

Olausson, P., Jentsch, J.D., Taylor, J.R. Repeated nicotine exposure enhances responding with conditioned reinforcement. Psychopharmacology (Berlin). 173 98, 2004. 

Rukstalis, M., Jepson, C., Strasser, A. et al. Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm. Psychopharmacology (Berlin). 180 41, 2005. 

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