Nicotine withdrawal from

Withdrawal from nicotine is treated in the outpatient setting. Symptomatic detoxification from nicotine is achieved with any single or combination of NRTs. Additional nonnicotine medications such as bupropion, nortriptyline, and clonidine may be helpful to reduce craving and various other withdrawal symptoms. Including a behavioral therapy component increases abstinence rates when combined with pharmacologic treatment. 

Given that there is strong evidence for a genetic component to tobacco addiction the identification of genes that may be responsible for this link leads to exciting new opportunities to help people to withdraw from nicotine and to prevent relapse. 

Similarly opioid peptides are important in nicotine addiction and may have a role in causing nicotine withdrawal symptoms in some smokers [35]. Opioid antagonists such as naltrexone are licensed treatments for dependence syndromes arising from other addictive drugs and could also be of use in some smokers to aid nicotine withdrawal [59] although there is no definitive evidence overall that they are beneficial [60]. 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

Watkins SS, Koob GF, Markou A (2000) Neural mechanisms underlying nicotine addiction acute positive reinforcement and withdrawal. Nicotine Tob Res 2 19-37 West RJ, Russell MA (1985) Effects of withdrawal from long-term nicotine gum use. Psychol Med 15 891-893... 

Naloxone precipitation, nnlike nicotine-antagonist challenge, fails to decrease DA-activity, yet still precipitates somatic signs (Carboni et al. 2000). Thus the aversiveness of nicotine withdrawal can be dissociated in part from those effects on the mesolimbic-DA reinforcement pathway that have sometimes been proposed to account for the affective aspects of withdrawal (Balfour 2004 Paterson et al. 2007). 

Mec-precipitated somatically expressed withdrawal behaviors Hippocampal slice from rats in spontaneous withdrawal Spontaneous withdrawal from cigarette smoking Spontaneous withdrawal from nicotine self-administration Spontaneous withdrawal... 

The pattern of data on the role of al receptors (pentamers of the al subunit) is far from clear. Nomikos et al. (1999) reported sharply reduced locomotor activity in nicotine-dependent rats injected with the selective al antagonist methyl-lycaconitine (MLA). Barik and Wonnacott (2006) found increased al sensitivity in the hippocampus of rats during nicotine withdrawal, as evidence by increased norepinephrine release in response to an al agonist. On the other hand, Markou and Paterson (2001) reported that systemically administered ML A failed to precipitate either somatically expressed withdrawal behaviors or altered ICSS thresholds. 

There have been few studies of acetylcholine release during nicotine withdrawal. Rada et al. (2001) found that withdrawal from continuous nicotine infusion resulted in significantly increased acetylcholine release in the NAcc, concomitant with somatically expressed withdrawal behaviors. This was similar to the effect of morphine withdrawal on NAcc acetylcholine release. Since dopamine release was decreased at the same time, the transmitter balance in the NAcc was radically altered. 

It is well established that nicotine stimulation of the mesolimbic dopamine (DA) pathway is essential to the reinforcing action of nicotine (Balfour 2004 Corrigall and Coen 1991). Considerable evidence suggests that alterations in this pathway may also be essential to the nicotine abstinence syndrome, particularly to its depression-like dimension. During withdrawal from continuous nicotine infusion, rats displayed reduced activity levels and reduced DA content in the striatum... 

Several natural products have been evaluated in rodent models of nicotine withdrawal. An extract of Hypericum perforatum (St. John s Wort, a putative antidepressant, and inhibitor of serotonin reuptake) reversed somatically expressed withdrawal behaviors and locomotor depression in spontaneous withdrawal (Catania et al. 2003). A benzoflavone compound isolated from Passiflora incarnata, interfered with the induction of physical dependence. Coadministration with chronic nicotine prevented various subsequent indicators of withdrawal syndrome in the mouse, including jumping, locomotor inactivity, immobility in the swim test and naloxone-precipitated escape jumping (Dhawan et al. 2002). 

CorrigaU WA, Coen KM (1991) Selective dopamine antagonists reduce nicotine selfadministration. Psychopharmacology 104 171-176 Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, lyers MB (1990a) Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse. Pharmacol Biochem Behav 36 339-344... 

Jonkman S, Markou A (2006) Blockade of nicotinic acetylcholine or dopamine D 1-fike receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminads does not precipitate nicotine withdrawal in nicotine-dependent rats, Neurosci Lett 400 140-145 Katsura M, Shuto K, Mohri Y, Tsujimura A, Ohkuma S (2001) Withdrawal from nicotine facilitates diazepam binding inhibitor mRNA expression in mouse cerebral cortex. Brain Res Mol Brain Res 97 194-218... 

Wilmouth CE, Spear LP (2006) Withdrawal from chronic nicotine in adolescent and adult rats. Pharmacol Biochem Behav 85 648-657... 

Tennant FS, Tarver AL, Rawason RA (1983) Clinical evaluation of mecamylamine for withdrawal from nicotine dependence. In Harris LS (ed) Problems of drug dependence, NIDA Research Monograph 49. USDHHS publication no, 84-1316, pp 239-246 Tercyak KP, Herman C, Audrain J (2002) Association of attention-deficit/hyperactivity disorder symptoms with levels of cigarette smoking in a community sample of adolescents, J Am Acad Child Adolesc Psychiatry 41 799-805... 

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