Abstract
Simple, rapid and inexpensive rodent models of nicotine physical dependence and withdrawal syndrome have proved useful for preliminary screening of smoking cessation treatments. They have led to an exponential increase of knowledge regarding the underlying neurobiological mechanisms of dependence and withdrawal syndrome. The human nicotine withdrawal syndrome in smoking cessation is variable and multidimensional, involving irritability, anxiety, depression, cognitive and attentional impairments, weight gain, sleep disturbances, and craving for nicotine. Aside from sleep disturbances, analogous phenomena have been seen in rodent models using different measures of withdrawal intensity. It appears likely that different withdrawal phenomena may involve some partially divergent mechanisms. For example, depression-like phenomena may involve alterations in mechanisms such as the mesolimbic dopamine pathway from the ventral tegmen-tal area to the nucleus accumbens. Irritability and anxiety may involve alterations in endogenous opioid systems and other regions, such as the amygdala. This chapter reviews many additional anatomical, neurochemical, and developmental elements that impact nicotine physical dependence.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adams ML, Cicero TJ (1998) Nitric oxide mediates mecamylamine- and naloxone- precipitated nicotine withdrawal. Eur J Pharmacol 345:R1–R2
Adriani W, Granstrem O, Macri S, Izykenova G, Dambinova S, Laviola G (2004) Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine. Neuropsy-chopharmacology 29:869–878
American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), American Psychiatric Association, Washington, DC, pp 176–247
Andersson K, Fuxe K, Eneroth P, Jansson A, Härfstrand A (1989) Effects of withdrawal from chronic exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat. Naunyn Schmiedebergs Arch Pharmacol 339:387–96
Aricioglu-Kartal F, Kayir H, Tayfun UI (2003) Effects of harman and harmine on naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Life Sci 73:2363–2371
Balerio GN, Aso E, Berrendero F, Murtra P, Maldonado R (2004) Delta9- tetrahydrocanabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice. Eur J Neurosci 20:2737–2748
Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco Dependence. Curr Drug Targets CNS Neurol Disord 1:413–21
Balfour DJ (2004) The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6:899–912
Barik J, Wonnacott S (2006) Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices: interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69:618–628
Belluzzi JD, Lee AG, Oliff HS, Leslie FM (2004) Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology 174:389–395
Benowitz NL (1990) Pharmacokinetic considerations in understanding nicotine dependence. CIBA Found Symp 152:186–200
Benowitz NL, Kuyt F, Jacob P 3rd (1982) Circadian blood nicotine concentrations during cigarette smoking. Clin Pharmacol Ther 32:758–764
Berrendero F, Kieffer BL, Maldonado R (2002) Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in muopioid receptor knockout mice. J Neurosci 22:10935–10940
Berrendero F, Mendizábal V, Robledo P, Galeote L, Bilkei-Gorzo A, Zimmer A, Maldonado R (2005) Nicotineinduced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. J Neursci 25:1103–1112
Besheer J, Bevins RA (2003) Impact of nicotine withdrawal on novelty reward and related behaviors. Behav Neurosci 117:327–340
Besson M, David V, Suarez S, Cormier A, Cazala P, Changeux JP, Granon S (2006) Genetic dissociation of two behaviors associated with nicotine addiction: beta-2 containing nicotinic receptors are involved in nicotine reinforcement but not in withdrawal syndrome. Psychopharmacology 187:189–199
Biala G, Weglinska B (2005) Blockade of the expression of mecamylamine precipitated nicotine withdrawal by calcium channel antagonists. Pharmacol Res 51:483–488
Biala G, Budzyska B, Kruk M (2005) Naloxone precipitates nicotine abstinence syndrome and attenuates nicotine-induced antinociception in mice. Pharmacol Rep 57:755–760
Bishop C, Parker GC, Coscina DV (2002) Nicotine and its withdrawal alter feeding induce by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats. Psychopharmacology 162:265–272
Bohus B, Koolhaas JM, Luiten PG, Korte SM, Roozendaal B, Wiersma A (1996) The neurobiology of the central nucleus of the amygdala in relation to neuroendocrine and autonomic outflow. Prog Brain Res 107:447–460
Breslau N, Peterson EL (1996) Smoking cessation in young adults: age at initiation of cigarette smoking and other suspected influences. Am J Public Health 86:214–220
Bruijnzeel AW, Markou A (2004) Adaptations in cholinergic transmission in the ventral tegmental area associated with the affective signs of nicotine withdrawal in rats. Neuropharmacology 47:572–579
Bruijnzeel AW, Zislis G, Wilson C, Gold MS (2007) Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 32:955–963
Carboni E, Bortone L, Giua C, Di Chiara G (2000) Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats. Drug Alcohol Depend 58:93–102
Castañé A, Valjent E, Ledent C, Parmentier M, Maldonado R, Valverde O (2002) Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 43:857–867
Catania MA, Firenzuoli F, Crupi A, Mannucci C, Caputi AP, Calapai G (2003) Hypericum perforatum attenuates nicotine withdrawal signs in mice. Psychopharmacology 169:186–189
Cheeta S, Irvine EE, Kenny PJ, File SE (2001) The dorsal raphé nucleus is a crucial structure mediating nicotine's anxiolytic effects and the development of tolerance and withdrawal responses. Psychopharmacology 155:78–85
Cohen C, Bergis OE, Galli F, Lochead AW, Jegham S, Biton B, Leonardon J, Avenet P, Sgard F, Besnard F, Graham D, Coste A, Oblin A, Curet O, Voltz C, Gardes A, Caille D, Perrault G, George P, Soubrie P, Scatton B (2003) SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation. J Pharmacol Exp Ther 306:407–420
Concas A, Sogliano C, Porcu P, Marra C, Brundu A, Biggio G (2006) Neurosteroids in nicotine and morphine dependence. Psychopharmacology 186:281–292
Corrigall WA, Coen KM (1991) Selective dopamine antagonists reduce nicotine selfadministration. Psychopharmacology 104:171–176
Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB (1990a) Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse. Pharmacol Biochem Behav 36:339–344
Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB (1990b) Sites of action of ondansetron to inhibit withdrawal from drugs of abuse. Pharmacol Biochem Behav 36:97–104
Cryan JF, Bruijnzeel AW, Skjei KL, Markou A (2003) Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology 168:347–358
Damaj MI, Kao W, Martin BR (2003) Characterization of spontaneous and precipitated nicotine withdrawal in the mouse. J Pharmacol Exp Ther 307:526–534
Davis JA, Gould TJ (2007) Atomoxetine reverses nicotine withdrawal-associated deficits in contextual fear conditioning. Neuropsychopharmacology 32:2011–2009
Davis JA, James JR, Siegel SJ, Gould TJ (2005) Withdrawal from chronic nicotine adminstration impairs contextual fear conditioning in C57BL/6 mice. J Neurosci 25:8708–8713
Dellu M, Thorén P (1987) changes in sympathetic nerve activity during morphine abstinence in the rat. Acta Physiol Scand 130:47–54
Dhawan K, Kumar S, Sharma A (2002) Nicotine reversal effects of the benzoflavone moity from Passiflora incarnate Linneaus in mice. Addict Biol 7:435–441
Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314
Epping-Jordan MP, Watkins SS, Koob GF, Markou A (1998) Dramatic decreases in brain reward function during nicotine withdrawal. Nature 393:76–79
Fornari A, Pedrazzi P, Lippi G, Picciotto MR, Zoli M, Zini I (2007) Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in highfat fed mice. Neurosci Lett 411:72–76
Fung YK, Schmid MJ, Anderson TM, Lau YS (1996) Effects of nicotine withdrawal on central dopaminergic systems. Pharmacol Biochem Behav 53:635–640
Gilbert DG, Meliska CJ, Williams CL, Jensen RA (1992) Subjective correlates of cigarette smoking-induced elevations of peripheral betaendorphin and cortisol. Psychopharmacology 106:275–81
Göktalay G, Cavun S, Levendusky MC, Hamilton JR, Millington WR (2006) Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal. Eur J Pharmacol. 530:95–102
Grabus SD, Martin BR, Batman AM, Tyndale RF, Sellers E, Damaj MI (2005) Nicotine physical dependence and tolerance in the mouse following chronic oral administration. Psychopharmacology 178:183–192
Grunberg NE, Bowen DJ, Winders SE (1986) Effects of nicotine on body weight and food consumption in female rats. Psychopharmacology 90:101–105
Guilloux JP, David DJ, Guiard BP, Chenu F, Repérant C, Toth M, Bourin M, Gardier AM (2006) Blockade of 5-HT1A receptors by (+/−)-pindolol potentiates cortical 5-HT outflow, but not antidepressant-like activity of paroxetine: microdialysis and behavioral aproaches in 5-HT1A receptor knockout mice. Neuropsychopharmacology 31:2162–2172
Halladay AK, Schwartz M, Wagner GC, Iba MM, Sekowski A, Fisher H (1999) Efficacy of providing nicotine in a liquid diet to rats. Proc Soc Exp Biol Med 221:215–223
Harris CM, Emmett-Oglesby MW, Robinson NG, Lal H (1986) Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ). Psychopharmacology 90:85–89
Harrison AA, Liem YT, Markou A (2001) Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats. Neuropsychopharmacology 25:55–71
Helton DR, Modlin DL, Tizzano JP, Rasmussen K (1993) Nicotine withdrawal: a behavioral assessment using schedule controlled responding, locomotor activity and sensorimotor reactivity. Psychopharmacology 113:205–210
Hildebrand BE, Nomikos GG, Bondjers C, Nisell M, Svensson TH (1997) Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms. Psychopharmacology 129:348–356
Hildebrand BE, Nomikos GG, Hertel P, Schilström B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779:214–225
Hildebrand BE, Panagis G, Svensson TH, Nomikos GG (1999) Behavioral and biochemical manifestations of mecamylamine-precipitated nicotine withdrawal in the rat: role of nicotinic receptors in the ventral tegmental area. Neuropsychopharmacology 21:560–574
Hughes JR (2006) Clinical significance of tobacco withdrawal. Nicotine Tob Res 8:153–156
Hughes JR (2007a) Effects of abstinence from tobacco: etiology, animal models, epidemiology, and significance: a subjective review. Nicotine Tob Res 9:329–339
Hughes JR (2007b) Effects of abstinence from tobacco: valid symptoms and time course. Nicotine Tob Res 9:315–327
Hughes JR, Keely J, Naud S (2004) Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 99:29–38
Irvine EE, Cheeta S, File SE (1999) Time-course of changes in the social interaction test of anxiety following acute and chronic administration of nicotine. Behav Pharmacol 10:691–697
Ise Y, Narita M, Nagase H, Suzuki (2000) Modulation of opioidergic system on mecamylamine precipitated nicotine-withdrawal aversion in rats. Psychopharmacology 151:49–54
Ise Y, Narita M, Nagase H, Suzuki T (2002) Modulation of kappa-opioidergic sytems on mecamylamine-precipitated nicotine-withdrawal aversion in rats. Neurosci Lett 323:164–166
Isola R, Vogelsberg V, Wemlinger TA, Neff NH, Hadjiconstantinou M (1999) Nicotine abstinence in the mouse. Brain Res 850:189–196
Isola R, Zhang H, Duchemin AM, Tejwani GA, Neff NH, Hadjiconstantinou M (2002) Metenkephalin and preproenkephalin mRNA changes in the striatum of the nicotine abstinent mouse. Neurosci Lett 325:67–71
Jonkman S, Markou A (2006) Blockade of nicotinic acetylcholine or dopamine D1-like receptors in the central nucleus of the amygdala or the bed nucleus of the stria terminails 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
Kenny PJ, Markou A (2005) Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems. J Neurosci 25:6208–6212
Kenny PJ, File SE, Rattray M (2000) Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus. Brain Res Mol Brain Res 85:234–238
Kenny PJ, Gasparini F, Markou A (2003) Group II metabotropic and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function associated with nicotine withdrawal in rats. J Pharmacol Exp Ther 306: 1068–1076
Keyler DE, Hieda Y, St Peter J, Pentel PR (1999) Altered disposition of repeated nicotine doses in rats immunized against nicotine. Nicotine Tob Res 1:241–249
Konu O, Kane JK, Barrett T, Vawter MP, Chang R, Ma JZ, Donovan DM, Sharp B, Becker KG, Li MD (2001) Region-specific transcriptional response to chronic nicotine in rat brain. Brain Res 909:194–192
Kota D, Martin BR, Robinson SE, Damaj MI (2007) Nicotine dependence and reward differ between adolescent and adult male mice. J Pharmacol Exp Ther 322:399–407
Krishnan-Sarin S, Rosen MI, O'Malley SS (1999) Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence. Arch Gen Psychiatry 56:663–668
Lake JR, Cole MJ, Beck L, Malin DH (2002) Chronic co-infusion of mecamylamine with nicotine reduces nicotine dependence in the rat. Program no. 811.7, 2002 abstract viewer. Society for Neuroscience, Washington, DC
LeSage MG, Keyler DE, Shoeman D, Raphael D, Collins G, Pentel PR (2002) Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine. Pharmacol Biochem Behav 72:279–289
LeSage MG, Burroughs D, Pentel PR (2006) Effects of nicotine withdrawal on performance under a progressive-ratio schedule of sucrose pellet delivery in rats. Pharmacol Biochem Behav 83:585–591
Levin ED, Morgan MM, Galvez C, Ellison GD (1987) Chronic nicotine and withdrawal effects on body weight and food and water consumption in female rats. Physiol Behav 39:441–444
Lewis A, Miller JH, Lea RA (2007) Monoamine oxidase and tobacco dependence. Neurotoxicology 28:182–195
Liechti ME, Markou A (2007) Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats. Eur J Pharmacol 554:164–174
Lindblom N, de Villiers SH, Semenova S, Kalayanov G, Gordon S, Schilström B, Ohansson AM, Markou A, Svensson TH (2005) Active immunisation against nicotine blocks the reward facilitating effects of nicotine and partially prevents nicotine withdrawal in the rat as measured by dopamine output in the nucleus accumbens, brain reward thresholds and somatic signs. Naunyn Schmiedebergs Arch Pharmacol 372:182–194
Liu ZH, Jin WQ (2004) Decrease of ventral tegmental area dopamine neuronal activity in nicotine withdrawal rats. Neuroreport 15:1479–1481
Malin DH (2001) Nicotine dependence studies with a laboratory model. Pharmacol Biochem Behav 70:551–559
Malin DH, Lake JR, Hammond MV, Fowler DE, Rogillio RB, Brown SL, Sims JL, Leecraft BM, Yang HY (1990) FMRF-NH2-like mammalian octapeptide: possible role in opiate dependence and abstinence. Peptides 11:969–972
Malin DH, Lake JR, Newlin-Maultsby P, Roberts LK, Lanier JG, Carter VA, Cunningham JS, Wilson OB (1992) Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav 43:779–784
Malin DH, Lake JR, Carter VA, Cunningham JS, Wilson OB (1993a) Naloxone precipitates nicotine abstinence syndrome in the rat. Psychopharmacology 112:339–342
Malin DH, Lake JR, Arcangeli KR, Deshotel KD, Hausam DD, Witherspoon WE, Carter VA, Yang HY, Pal B, Burgess K (1993b) Subcutaneous injection of an analog of neuropeptide FF precipitates morphine abstinence syndrome. Life Sci 53:PL261–216
Malin DH, Lake JR, Carter VA, Cunningham JS, Hebert KM, Conrad DL, Wilson OB (1994) The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat. Psychopharmacology 115:180–184
Malin DH, Lake JR, Short PE, Blossman JB, Lawless BA, Schopen CK, Sailer EE, Burgess K, Wilson OB (1996a) Nicotine abstinence syndrome precipitated by an analog of neuropeptide FF. Pharmacol Biochem Behav 54:581–585
Malin DH, Lake JR, Payne MC, Short PE, Carter VA, Cunningham JS, Wilson OB (1996b) Nicotine alleviation of nicotine abstinence syndrome is naloxone-reversible. Pharmacol Biochem Behav 53:81–85
Malin DH, Lake JR, Schopen CK, Kirk JW, Sailer EE, Lawless BA, Upchurch TP, Shenoi M, Rajan N (1997) Nicotine abstinence syndrome precipitated by central but not peripheral hexamethonium. Pharmacol Biochem Behav 58:695–699
Malin DH, Lake JR, Upchurch TP, Shenoi M, Rajan N, Schweinle WE (1998a) Nicotine abstinence syndrome precipitated by the competitive nicotinic antagnist dihydro-beta-erythroidine. Pharmacol Biochem Behav 60:609–613
Malin DH, Lake JR, Shenoi M, Upchurch TP, Johnson SC, Schweinle WE, Cadle CD (1998b) The nitric oxide synthesis inhibitor nitro-L-arginine (L-NNA) attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 140:371–377
Malin DH, Lake JR, Lin A, Saldana M, Balch L, Irvin ML, Chandrasekara H, Alvarado CL, Hieda Y, Keyler DE, Pentel PR, Ennifar S, Basham LE, Naso R, Fattom A (2001) Passive immunization against nicotine prevents nicotine alleviation of nicotine abstinence syndrome. Pharmacol Biochem Behav 68:87–92
Malin DH, Alvarado CL, Woodhouse KS, Karp H, Urdiales E, Lay D, Appleby P, Moon W, Ennifar S, Basham L, Fattom A (2002) Passive immunization against nicotine attenuates nicotine discrimination. Life Sci 70:2793–2798
Malin DH, Lake JR, Smith TD, Khambati HN, Meyers-Paal RL, Montellano AL, Jennings RE, Erwin DS, Presley SE, Perales BA (2006) Bupropion attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 184:494–503
Mannucci C, Catania MA, Adamo EB, Bellomo M, Caputi AP, Calapai G (2005) Long term effects of high doses of nicotine on feeding behavior and brain nitric oxide synthase activity in female mice. J Pharmacol Sci 98:232–238
Mannucci C, Tedesco M, Bellomo M, Caputi AP, Calapai G (2006) Long-term effects of nicotine on the forced swimming test in mice: an experimental model for the study of depression caused by smoke. Neurochem Int 49:481–486
Markou A (2007) Metabotropic glutamate receptor antagonists: novel therapeutics for nicotine dependence and depression? Biol Psychiatry 61:17–22
Markou A, Paterson NE (2001) The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat. Nicotine Tob Res. 3:361–373
Marttila K, Raattamaa H, Ahtee L (2006) Effects of chronic nicotine administration and its withdrawal on striatal FosB/DeltaFosB and c-Fos expression in rats and mice. Neuropharmacology 51:44–51
Narita M, Funada M, Suzuki T (2001) Regulation of opioid dependence by opioid receptor types. Pharmacol Ther 89:1–15
Nomikos GG, Hildebrand BE, Panagis G, Svensson TH (1999) Nicotine withdrawal in the rat: role of alpha7 nicotinic receptors in the ventral tegmental area. Neuroreport 10:697–702
Nutt DJ, Glue P, Ball D (1991) Clinical features of drug tolerance and dependence. In: Pratt JA (ed) The biological bases of drug tolerance and dependence. Academic, New York, pp 29–44
O'Dell LE, Koob GF (2007) ‘Nicotine deprivation effect’ in rats with intermittent 23-hour access to intravenous nicotine self-administration. Pharmacol Biochem Behav 86:346–53
O'Dell LE, Bruijnzeel AW, Ghozland S, Markou A, Koob GF (2004) Nicotine withdrawal in adolescent and adult rats. Ann N Y Acad Sci 1021:167–174
O'Dell LE, Bruijnzeel AW, Smith RT, Parsons LH, Merves ML, Goldberger BA, Richardson HN, Koob GF, Markou A (2006) Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction. Psychopharmacology 186(4):612–619
O'Dell LE, Chen SA, Smith RT, Specio SE, Balster RL, Paterson NE, Markou A, Zorrilla EP, Koob GF (2007) Extended access to nicotine self-administration leads to dependence: Circa-dian measures, withdrawal measures, and extinction behavior in rats. JPharmacol Exp Ther 320:180–193
Panagis G, Hildebrand BE, Svensson TH, Nomikos GG (2000) Selective c-Fos induction and decreased dopamine release in the central nucleus of amygdala in rats displayng a mecamylamine-precipitated nicotine withdrawal syndrome. Synapse 35:15–25
Pandey SC, Xu T, Zhang D (1999) Regulation of AP-1 gene transcription factor binding activity in the rat brain during nicotine dependence. Neurosci Lett 264:21–24
Pandey SC, Roy A, Xu T, Mittal N (2001) Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain. J. Neurochem 7:943–952
Paterson NE, Markou A (2004) Prolonged nicotine dependence associated with extended access to nicotine self-administration in rats. Psychopharmacology 173:64–72
Paterson NE, Bruijnzeel AW, Kenny PJ, Wright CD, Froestl W, Markou A (2005) Prolonged nicotine exposure does not alter GABA(B) receptor-mediated regulation of brain reward function. Neuropharmacology 49:953–967
Paterson NE, Balfour DJ, Markou A (2007) Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell. Eur J Neurosci 25:3099–3108
Pentel PR, Malin DH, Ennifar S, Hieda Y, Keyler DE, Lake JR, Milstein JR, Basham LE, Coy RT, Moon JW, Naso R, Fattom A (2000) A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav 65:191–198
Piasecki TM, Niaura R, Shadel WG, Abrams D, Goldstein M, Fiore MC, Baker TB (2000) Smoking withdrawal dynamics in unaided quitters. J Abnorm Psychol 109(1):74–86
Piasecki TM, Jorenby DE, Smith SS, Fiore MC, Baker TB (2003) Smoking withdrawal dynamics: II. Improved tests of withdrawal-relapse relations. J Abnorm Psychol 112:14–27
Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, Fuxe K, Changeux JP (1998) Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173–177
Pietilä K, Lähde T, Attila M, Ahtee L, Nordberg A (1998) Regulation of nicotinic receptors in the brain of mice withdrawn from chronic oral nicotine treatment. Naunyn Schmiedebergs Arch Pharmacol 357:176–182
Pluzarev O, Pandey SC (2004) Modulation of CREB expression and phosphorylation in the rat nucleus accumbens during nicotine exposure and withdrawal. J Neurosci Res 77:884–891
Pogun S, Demirgoren S, Taskiran D, Kanit L, Yilmaz O, Koylu EO, Balkan B, London ED (2000) Nicotine modulates nitric oxide in rat brain. Eur Neuropsychopharmacol 10:463–472
Polesskaya OO, Fryxell KJ, Merchant AD, Locklear LL, Ker KF, McDonald CG, Eppolito AK, Smith LN, Wheeler TL, Smith RF (2007) Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain. Neurotoxicol Teratol 29:126–140
Rada P, Jensen K, Hoebel BG (2001) Effects of nicotine and mecamylamine-induced withdrawal on extracellular dopamine and acetylcholine in the rat nucleus accumbens. Psychopharmacology 157:105–110
Rahman S, Zhang J, Engleman EA, Corrigall WA (2004) Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a micro-dialysis study. Neuroscience 129:415–424
Rasmussen K, Czachura JF (1995) Nicotine withdrawal leads to increased firing rates of midbrain dopamine neurons. Neuroreport 7:329–332
Rasmussen K, Calligaro DO, Czachura JF, Dreshfield-Ahmad LJ, Evans DC, HemRick-Luecke SK, Kallman MJ, Kendrick WT, Leander JD, Nelson DL, Overshiner CD, Wainscott DB, Wolff MC, Wong DT, Branchek TA, Zgombick JM, Xu YC (2000) The novel 5-hydroxytryptamine(1A) antagonist LY426965: effects on nicotine withdrawal and interactions with fluoxetine. J Pharmacol Exp Ther 294:688–700
Ribeiro EB, Bettiker RL, Bogdanov M, Wurtman RJ (1993) Effects of systemic nicotine on serotonin release in rat brain. Brain Res 621:311–318
Salas R, Pieri F, De Biasi M (2004) Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J Neurosci 24:10035–10039
Salminen O, Seppä T, Gäddnäs H, Ahtee L (1999) The effects of acute nicotine on the metabolism of dopamine and the expression of Fos protein in striatal and limbic brain areas of rats during chronic nicotine infusion and its withdrawal. J Neurosci 19:8145–8151
Salmon AM, Evrard A, Damaj I, Changeux JP (2004) Reduction of withdrawal signs after chronic nicotine exposure of alpha-calcitonin generelated peptide knockout mice. Neurosci Lett 360:73–76
Schmidt BL, Tambeli CH, Gear RW, Levine JD (2001) Nicotine withdrawal hyperalgesia and opioidmediated analgesia depend on nicotine receptors in nucleus accumbens. Neuroscience 106:129–136
Semba J, Wakuta M, Maeda J, Suhara T (2004) Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats: implications for precipitation of depression during smoking cessation. Psychoneuroendocrinology 29:215–226
Semenova S, Markou A (2003) Clozapine treatment attenuated somatic and affective signs of nicotine and amphetamine withdrawal in subsets of rats exhibiting hyposensitivity to the initial effects of clozapine. Biol Psychiatry 54:1249–1264
Semenova S, Bespalov A, Markou A (2003) Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration. Eur J Pharmacol 472:99–110
Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J (2000) The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology 148:33–40
Shoaib M, Bizarro L (2005) Deficits in a sustained attention task following nicotine withdrawal in rats. Psychopharmacology 178:211–222
Shoaib M, Lowe AS, Williams SC (2004) Imaging localized dynamic changes in the nucleus accumbens following nicotine withdrawal in rats. Neuroimage 22:847–854
Siggins GR, Martin G, Roberto M, Nie Z, Madamba S, De Lecea L (2003) Glutamatergic transmission in opiate and alcohol dependence. Ann N Y Acad Sci 1003:196–211
Skjei KL, Markou A (2003) Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats. Psychopharmacology 168:280–292
Suemaru K, Araki H, Kitamura Y, Yasuda K, Gomita Y (2001) Cessation of chronic nicotine administration enhances wetdog shake responses to 5-HT2 receptor stimulation in rats. Psychopharmacology 159:38–41
Suh HW, Hudson PM, McMillian MK, Das KP, Wilson BC, Wu GC, Hong JS (1995) Longterm stimulation of nicotinic receptors is required to increase proenkephalin AmRNA levels and the delayed secretion of [Met5]-enkephalin in bovine adrenal medullary chromaffin cells. J Pharmacol Exp Ther 275:1663–1670
Suzuki T, Ise Y, Tsuda M, Maeda J, Misawa M (1996) Mecamylamine-precipitated nicotine-withdrawal aversion in rats. Eur J Pharmacol 314:281–284
Suzuki T, Ise Y, Mori T, Misawa M (1997) Attenuation of mecamylamine-precipitated nicotine-withdrawal aversion by the 5-HT3 receptor antagonist ondansetron. Life Sci 61:PL249–254
Tzavara ET, Monory K, Hanoune J, Nomikos GG (2002) Nicotine withdrawal syndrome: behavioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala. Eur J Neurosci 16:149–153
Vann RE, Balster RL, Beardsley PM (2006) Dose, duration, and pattern of nicotine adminstration as determinants of behavioral dependence in rats. Psychopharmacology 184:482–93
Vastola BJ, Douglas LA, Varlinskaya EI, Spear LP (2002) Nicotine-induced conditioned place preference in adolescent and adult rats. Physiol Behav 77:107–114
Watkins SS, Stinus L, Koob GF, Markou A (2000) Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. J Pharmacol Exp Ther 292:1053–1064
Wilmouth CE, Spear LP (2006) Withdrawal from chronic nicotine in adolescent and adult rats. Pharmacol Biochem Behav 85:648–657
Xiang XN, Wang HL, Wu WR, Cao DV, Wang HS, Zhao Y (2006) Ethological analysis of scopo-lamine pretreatment in morphine dependent rats. Physiol Behav 88:183–90
Yasuda K, Suemaru K, Araki H, Gomita Y (2002) Effect of nicotine cessation on the central sero-tonergic systems in mice involvement of 5-HT(2) receptors. Naunyn Schmiedbergs Arch Pharmacol 366:276–281
Zarevics P, Setler PE (1979) Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation: evidence for the direct involvement of dopamine in brain reinforcement mechanisms. Brain Res 169:499–512.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Malin, D.H., Goyarzu, P. (2009). Rodent Models of Nicotine Withdrawal Syndrome. In: Henningfield, J.E., London, E.D., Pogun, S. (eds) Nicotine Psychopharmacology. Handbook of Experimental Pharmacology, vol 192. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69248-5_14
Download citation
DOI: https://doi.org/10.1007/978-3-540-69248-5_14
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-69246-1
Online ISBN: 978-3-540-69248-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)