Diminished Nicotine Withdrawal in Adolescent Rats: Implications for Vulnerability to Addiction

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2006 Apr 7

PMID 16598454

Citations 89

Authors

Laura E ODell

Adie W Bruijnzeel

Ron T Smith

Loren H Parsons

Michele L Merves

Bruce A Goldberger

Heather N Richardson

George F Koob

Athina Markou

Affiliations

Soon will be listed here.

Abstract

Rationale: Enhanced reinforcing effects of nicotine during adolescence appear to contribute to the rapid development of dependence in this age group. However, the contribution of nicotine withdrawal to dependence in adolescents is unclear.

Objective: We compared motivational and somatic signs of nicotine withdrawal in adolescent and adult rats.

Materials And Methods: In experiment 1, motivational signs of nicotine withdrawal were compared using intracranial self-stimulation procedures after administration of mecamylamine (1.5 mg/kg, i.p.) in adolescent and adult rats made dependent on nicotine (9 mg/kg/day). Somatic signs of withdrawal were compared in two experiments using various doses of nicotine (adolescent doses: 0, 1.6, 3.2, 4.7 mg/kg/day; adult doses: 0, 1, 2.1, 3.2 mg/kg/day, expressed as nicotine base) to produce dependence and one dose of mecamylamine (1.5 mg/kg, i.p.) to precipitate withdrawal (experiment 2) and in a subsequent experiment, using various doses of mecamylamine (0, 0.75, 1.5, 3.0 mg/kg, i.p.) to precipitate withdrawal and a dose of nicotine (adolescent dose: 4.7 mg/kg/day; adult dose: 3.2 mg/kg/day) that produced equivalent nicotine blood levels in these age groups (experiment 3).

Results: Adolescents did not display the decreases in brain reward function observed in adults experiencing withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to adults regardless of the dosing procedure used.

Conclusion: The negative effects of nicotine withdrawal are lower during adolescence relative to later periods of development. Both the enhanced rewarding effects and the diminished nicotine withdrawal likely contribute to the rapid development of nicotine use during adolescence.

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References

Sofuoglu M, Kosten T . Pharmacologic management of relapse prevention in addictive disorders. Psychiatr Clin North Am. 2004; 27(4):627-48. DOI: 10.1016/j.psc.2004.06.002. View

Vastola B, Douglas L, Varlinskaya E, Spear L . Nicotine-induced conditioned place preference in adolescent and adult rats. Physiol Behav. 2002; 77(1):107-14. DOI: 10.1016/s0031-9384(02)00818-1. View

Hildebrand B, Svensson T . Intraaccumbal mecamylamine infusion does not affect dopamine output in the nucleus accumbens of chronically nicotine-treated rats. J Neural Transm (Vienna). 2000; 107(8-9):861-72. DOI: 10.1007/s007020070038. View

Watkins S, Stinus L, Koob G, Markou A . Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. J Pharmacol Exp Ther. 2000; 292(3):1053-64. View

Skjei K, Markou A . Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats. Psychopharmacology (Berl). 2003; 168(3):280-92. DOI: 10.1007/s00213-003-1414-1. View

McDonald J, Johnston M . Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res Brain Res Rev. 1990; 15(1):41-70. DOI: 10.1016/0165-0173(90)90011-c. View

Smith T, House Jr R, Croghan I, Gauvin T, Colligan R, Offord K . Nicotine patch therapy in adolescent smokers. Pediatrics. 1996; 98(4 Pt 1):659-67. View

de Graaf-Peters V, Hadders-Algra M . Ontogeny of the human central nervous system: what is happening when?. Early Hum Dev. 2005; 82(4):257-66. DOI: 10.1016/j.earlhumdev.2005.10.013. View

DiFranza J, Wellman R . Preventing cancer by controlling youth tobacco use. Semin Oncol Nurs. 2004; 19(4):261-7. DOI: 10.1053/j.soncn.2003.08.003. View

10.

Taioli E, Wynder E . Effect of the age at which smoking begins on frequency of smoking in adulthood. N Engl J Med. 1991; 325(13):968-9. DOI: 10.1056/NEJM199109263251318. View

11.

Di Chiara G . Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol. 2000; 393(1-3):295-314. DOI: 10.1016/s0014-2999(00)00122-9. View

12.

Trauth J, Seidler F, Slotkin T . An animal model of adolescent nicotine exposure: effects on gene expression and macromolecular constituents in rat brain regions. Brain Res. 2000; 867(1-2):29-39. DOI: 10.1016/s0006-8993(00)02208-3. View

13.

Suzuki T, Ise Y, Tsuda M, Maeda J, Misawa M . Mecamylamine-precipitated nicotine-withdrawal aversion in rats. Eur J Pharmacol. 1996; 314(3):281-4. DOI: 10.1016/s0014-2999(96)00723-6. View

14.

Wilmouth C, Spear L . Adolescent and adult rats' aversion to flavors previously paired with nicotine. Ann N Y Acad Sci. 2004; 1021:462-4. DOI: 10.1196/annals.1308.065. View

15.

ODell L, Bruijnzeel A, Ghozland S, Markou A, Koob G . Nicotine withdrawal in adolescent and adult rats. Ann N Y Acad Sci. 2004; 1021:167-74. DOI: 10.1196/annals.1308.022. View

16.

Koob G, Moal M . Plasticity of reward neurocircuitry and the 'dark side' of drug addiction. Nat Neurosci. 2005; 8(11):1442-4. DOI: 10.1038/nn1105-1442. View

17.

Torrella T, Badanich K, Philpot R, Kirstein C, Wecker L . Developmental differences in nicotine place conditioning. Ann N Y Acad Sci. 2004; 1021:399-403. DOI: 10.1196/annals.1308.052. View

18.

Kenny P, Markou A . Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems. J Neurosci. 2005; 25(26):6208-12. PMC: 6725046. DOI: 10.1523/JNEUROSCI.4785-04.2005. View

19.

Belluzzi J, Lee A, Oliff H, Leslie F . Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology (Berl). 2004; 174(3):389-95. DOI: 10.1007/s00213-003-1758-6. View

20.

Hildebrand B, Nomikos G, Hertel P, Schilstrom B, Svensson T . 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. 1998; 779(1-2):214-25. DOI: 10.1016/s0006-8993(97)01135-9. View