Skip to main content

Advertisement

Log in

Age differences in the spontaneous acquisition of nicotine self-administration in male Wistar and Long–Evans rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Epidemiological evidence suggests that adolescents may exhibit a unique susceptibility to the motivational effects of nicotine compared to adults. In contrast to the hypothesis of an enhanced vulnerability to nicotine during adolescence, we have observed that nicotine is less reinforcing in adolescent compared to adult rats using a progressive ratio reinforcement schedule in an operant self-administration procedure, although prior operant conditioning experience may have masked differences in initial sensitivity to nicotine.

Objectives

This study examined the spontaneous acquisition of nicotine self-administration in adolescent (postnatal day (PD) 31) and adult (PD87) male Wistar and Long–Evans rats.

Materials and methods

Rats self-administered nicotine (0.015 or 0.03 mg/kg/infusion, i.v.) during 2-h operant conditioning sessions under fixed-ratio-1 (FR1) and FR3 reinforcement schedules for six sessions each. A subset of rats (adolescents: PD42, adults: PD98) underwent extinction of responding and nicotine priming-induced reinstatement (0.15 mg/kg, s.c.). In a separate group of rats, saccharin self-administration (0.1 ml of 0.2% w/v) was tested to determine the specificity of our findings with nicotine.

Results

A greater proportion of adult compared to adolescent rats acquired self-administration of 0.015 mg/kg/infusion nicotine, but both age groups readily acquired self-administration of 0.03 mg/kg/infusion nicotine and saccharin. Age differences in extinction of responding for nicotine or saccharin depended upon strain, but priming-induced reinstatement was similar across age and strain.

Conclusions

The current findings are consistent with those obtained under a more demanding progressive ratio reinforcement schedule and suggest that adolescents, compared to adults, may not be as sensitive to the reinforcing effects of nicotine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adriani W, Laviola G (2003) Elevated levels of impulsivity and reduced place conditioning with d-amphetamine: two behavioral features of adolescence in mice. Behav Neurosci 117:695–703

    Article  PubMed  CAS  Google Scholar 

  • Adriani W, Chiarotti F, Laviola G (1998) Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice. Behav Neurosci 112:1152–1166

    Article  PubMed  CAS  Google Scholar 

  • Adriani W, Macri S, Pacifici R, Laviola G (2002) Peculiar vulnerability to nicotine oral self-administration in mice during early adolescence. Neuropsychopharmacology 27:212–224

    Article  PubMed  CAS  Google Scholar 

  • Agrawal A, Grant JD, Waldron M, Duncan AE, Scherrer JF, Lynskey MT, Madden PA, Bucholz KK, Heath AC (2006) Risk for initiation of substance use as a function of age of onset of cigarette, alcohol and cannabis use: findings in a Midwestern female twin cohort. Prev Med 435:125–128

    Article  Google Scholar 

  • Arnett J (1992) Reckless behavior in adolescence: a developmental perspective. Deve Rev 12:339–373

    Article  Google Scholar 

  • Azam L, Chen Y, Leslie FM (2007) Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons. Neuroscience 144:1347–1360

    Article  PubMed  CAS  Google Scholar 

  • Badanich KA, Adler KJ, Kirstein CL (2006) Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi. Eur J Pharmacol 550:95–106

    Article  PubMed  CAS  Google Scholar 

  • Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43

    Article  CAS  Google Scholar 

  • Barr CS, Schwandt ML, Newman TK, Higley JD (2004) The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic, and psychological variables. Ann N Y Acad Sci 1021:221–233

    Article  PubMed  CAS  Google Scholar 

  • Bechara A, Nader K, van der Kooy D (1998) A two-separate-motivational-systems hypothesis of opioid addiction. Pharmacol Biochem Behav 59:1–17

    Article  PubMed  CAS  Google Scholar 

  • Belluzzi JD, Lee AG, Oliff HS, Leslie FM (2004) Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology (Berl) 174:389–395

    Article  CAS  Google Scholar 

  • Belluzzi JD, Wang R, Leslie FM (2005) Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705–712

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC (1996) Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 20:1–25

    Article  PubMed  CAS  Google Scholar 

  • Bolanos CA, Garmsen GM, Clair MA, McDougall SA (1996) Effects of the kappa-opioid receptor agonist U-50,488 on morphine-induced place preference conditioning in the developing rat. Eur J Pharmacol 317:1–8

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Brielmaier JM, McDonald CG, Smith RF (2007) Immediate and long-term behavioral effects of a single nicotine injection in adolescent and adult rats. Neurotoxicol Teratol 29:74–80

    Article  PubMed  CAS  Google Scholar 

  • Brioni JD, O’Neill AB, Kim DJ, Buckley MJ, Decker MW, Arneric SP (1994) Anxiolytic-like effects of the novel cholinergic channel activator ABT-418. J Pharmacol Exp Ther 271:353–361

    PubMed  CAS  Google Scholar 

  • Chambers RA, Taylor JR, Potenza MN (2003) Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 160:1041–1052

    Article  PubMed  Google Scholar 

  • Chen J, Millar WJ (1998) Age of smoking initiation: implications for quitting. Health Rep 9:39–46(Eng) 39–48(Fre)

    PubMed  CAS  Google Scholar 

  • Chen H, Matta SG, Sharp BM (2007) Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug. Neuropsychopharmacology 32:700–709

    Article  PubMed  CAS  Google Scholar 

  • Chiamulera C, Borgo C, Falchetto S, Valerio E, Tessari M (1996) Nicotine reinstatement of nicotine self-administration after long-term extinction. Psychopharmacology (Berl) 127:102–107

    Article  CAS  Google Scholar 

  • Colby SM, Tiffany ST, Shiffman S, Niaura RS (2000) Are adolescent smokers dependent on nicotine? A review of the evidence. Drug Alcohol Depend 59(Suppl 1):S83–S95

    Article  PubMed  Google Scholar 

  • Corrigall WA, Coen KM (1989) Nicotine maintains robust self-administration in rats on a limited-access schedule. Psychopharmacology (Berl) 99:473–478

    Article  CAS  Google Scholar 

  • Cruz FC, Delucia R, Planeta CS (2005) Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats. Pharmacol Biochem Behav 80:411–417

    Article  PubMed  CAS  Google Scholar 

  • Deminiere JM, Piazza PV, Le Moal M, Simon H (1989) Experimental approach to individual vulnerability to psychostimulant addiction. Neurosci Biobehav Rev 13:141–147

    Article  PubMed  CAS  Google Scholar 

  • Department of Health and Human Services U.S.A. (1994) Preventing tobacco use among young people: a report from the Surgeon General. Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA

    Google Scholar 

  • Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314

    Article  PubMed  Google Scholar 

  • Donny EC, Caggiula AR, Knopf S, Brown C (1995) Nicotine self-administration in rats. Psychopharmacology (Berl) 122:390–394

    Article  CAS  Google Scholar 

  • Donny EC, Lanza ST, Balster RL, Collins LM, Caggiula A, Rowell PP (2004) Using growth models to relate acquisition of nicotine self-administration to break point and nicotinic receptor binding. Drug Alcohol Depend 75:23–35

    Article  PubMed  CAS  Google Scholar 

  • Douglas LA, Varlinskaya EI, Spear LP (2003) Novel-object place conditioning in adolescent and adult male and female rats: effects of social isolation. Physiol Behav 80:317–325

    Article  PubMed  CAS  Google Scholar 

  • Dworkin SI, Mirkis S, Smith JE (1995) Response-dependent versus response-independent presentation of cocaine: differences in the lethal effects of the drug. Psychopharmacology (Berl) 117:262–266

    Article  CAS  Google Scholar 

  • Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl) 189:1–16

    Article  CAS  Google Scholar 

  • Fibiger HC, Phillips AG (1988) Mesocorticolimbic dopamine systems and reward. Ann N Y Acad Sci 537:206–215

    Article  PubMed  CAS  Google Scholar 

  • Frantz KJ, O’Dell LE, Parsons LH (2007) Behavioral and neurochemical responses to cocaine in periadolescent and adult rats. Neuropsychopharmacology 32:625–637

    Article  PubMed  CAS  Google Scholar 

  • Grant BF, Dawson DA (1998) Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abuse 10:163–173

    Article  PubMed  CAS  Google Scholar 

  • Hanna EZ, Yi HY, Dufour MC, Whitmore CC (2001) The relationship of early-onset regular smoking to alcohol use, depression, illicit drug use, and other risky behaviors during early adolescence: results from the youth supplement to the third national health and nutrition examination survey. J Subst Abuse 13:265–282

    Article  PubMed  CAS  Google Scholar 

  • Homberg JR, van den Akker M, Raaso HS, Wardeh G, Binnekade R, Schoffelmeer AN, de Vries TJ (2002) Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci 15:1542–1550

    Article  PubMed  Google Scholar 

  • Infurna RN, Spear LP (1979) Developmental changes in amphetamine-induced taste aversions. Pharmacol Biochem Behav 11:31–35

    Article  PubMed  CAS  Google Scholar 

  • Irvine EE, Bagnalasta M, Marcon C, Motta C, Tessari M, File SE, Chiamulera C (2001) Nicotine self-administration and withdrawal: modulation of anxiety in the social interaction test in rats. Psychopharmacology (Berl) 153:315–320

    Article  CAS  Google Scholar 

  • Jacobs EH, Smit AB, de Vries TJ, Schoffelmeer AN (2003) Neuroadaptive effects of active versus passive drug administration in addiction research. Trends Pharmacol Sci 24:566–573

    Article  PubMed  CAS  Google Scholar 

  • Kantak KM, Goodrich CM, Uribe V (2007) Influence of sex, estrous cycle, and drug-onset age on cocaine self-administration in rats (Rattus norvegicus). Exp Clin Psychopharmacol 15:37–47

    Article  PubMed  CAS  Google Scholar 

  • Kyerematen GA, Owens GF, Chattopadhyay B, deBethizy JD, Vesell ES (1988) Sexual dimorphism of nicotine metabolism and distribution in the rat. Studies in vivo and in vitro. Drug Metab Dispos 16:823–828

    PubMed  CAS  Google Scholar 

  • Laviola G, Adriani W, Morley-Fletcher S, Terranova ML (2002) Peculiar response of adolescent mice to acute and chronic stress and to amphetamine: evidence of sex differences. Behav Brain Res 130:117–125

    Article  PubMed  CAS  Google Scholar 

  • Laviola G, Macri S, Morley-Fletcher S, Adriani W (2003) Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence. Neurosci Biobehav Rev 27:19–31

    Article  PubMed  Google Scholar 

  • Lê AD, Li Z, Funk D, Shram M, Li TK, Shaham Y (2006) Increased vulnerability to nicotine self-administration and relapse in alcohol-naive offspring of rats selectively bred for high alcohol intake. J Neurosci 26:1872–1879

    Article  PubMed  CAS  Google Scholar 

  • Lecca D, Cacciapaglia F, Valentini V, Acquas E, Di Chiara G (2007) Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat. Psychopharmacology (Berl) 191:653–667

    Article  CAS  Google Scholar 

  • Levin ED, Rezvani AH, Montoya D, Rose JE, Swartzwelder HS (2003) Adolescent-onset nicotine self-administration modeled in female rats. Psychopharmacology (Berl) 169:141–149

    Article  CAS  Google Scholar 

  • Levin ED, Lawrence SS, Petro A, Horton K, Rezvani AH, Seidler FJ, Slotkin TA (2007) Adolescent vs. adult-onset nicotine self-administration in male rats: duration of effect and differential nicotinic receptor correlates. Neurotoxicol Teratol 2:2

    Google Scholar 

  • Macri S, Adriani W, Chiarotti F, Laviola G (2002) Risk taking during exploration of a plus-maze is greater in adolescent than in juvenile or adult mice. Anim Behav 64:541–546

    Article  Google Scholar 

  • Maldonado AM, Kirstein CL (2005) Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats. Physiol Behav 86:568–572

    Article  PubMed  CAS  Google Scholar 

  • Marks MJ, Campbell SM, Romm E, Collins AC (1991) Genotype influences the development of tolerance to nicotine in the mouse. J Pharmacol Exp Ther 259:392–402

    PubMed  CAS  Google Scholar 

  • 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 (Berl) 186:612–619

    Article  CAS  Google Scholar 

  • O’Dell LE, Torres OV, Natividad LA, Tejeda HA (2007a) Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats. Neurotoxicol Teratol 29:17–22

    Article  PubMed  CAS  Google Scholar 

  • O’Dell LE, Chen SA, Smith RT, Specio SE, Balster RL, Paterson NE, Markou A, Zorrilla EP, Koob GF (2007b) Extended access to nicotine self-administration leads to dependence: Circadian measures, withdrawal measures, and extinction behavior in rats. J Pharmacol Exp Ther 320:180–193

    Article  PubMed  CAS  Google Scholar 

  • Piazza PV, Deminiere JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513

    Article  PubMed  CAS  Google Scholar 

  • Piazza PV, Rouge-Pont F, Deminiere JM, Kharoubi M, Le Moal M, Simon H (1991) Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration. Brain Res 567:169–174

    Article  PubMed  CAS  Google Scholar 

  • Pidoplichko VI, Noguchi J, Areola OO, Liang Y, Peterson J, Zhang T, Dani JA (2004) Nicotinic cholinergic synaptic mechanisms in the ventral tegmental area contribute to nicotine addiction. Learn Mem 11:60–69

    Article  PubMed  Google Scholar 

  • Pontieri FE, Tanda G, Orzi F, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257

    Article  PubMed  CAS  Google Scholar 

  • Poulos CX, Lê AD, Parker JL (1995) Impulsivity predicts individual susceptibility to high levels of alcohol self-administration. Behav Pharmacol 6:810–814

    Article  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Schenk S, Lacelle G, Gorman K, Amit Z (1987) Cocaine self-administration in rats influenced by environmental conditions: implications for the etiology of drug abuse. Neurosci Lett 81:227–231

    Article  PubMed  CAS  Google Scholar 

  • Schenk S, Robinson B, Amit Z (1988) Housing conditions fail to affect the intravenous self-administration of amphetamine. Pharmacol Biochem Behav 31:59–62

    Article  PubMed  CAS  Google Scholar 

  • Scheufele PM, Faraday MM, Grunberg NE (2000) Nicotine administration interacts with housing conditions to alter social and non-social behaviors in male and female Long–Evans rats. Nicotine Tob Res 2:169–178

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Adamson LK, Grocki S, Corrigall WA (1997) Reinstatement and spontaneous recovery of nicotine seeking in rats. Psychopharmacology (Berl) 130:396–403

    Article  CAS  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    Article  CAS  Google Scholar 

  • Shoaib M, Stolerman IP (1999) Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats. Psychopharmacology (Berl) 143:318–321

    Article  CAS  Google Scholar 

  • Shoaib M, Schindler CW, Goldberg SR (1997) Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition. Psychopharmacology (Berl) 129:35–43

    Article  CAS  Google Scholar 

  • Shram MJ, Funk D, Li Z, Lê AD (2006) Periadolescent and adult rats respond differently in tests measuring the rewarding and aversive effects of nicotine. Psychopharmacology (Berl) 186:201–208

    Article  CAS  Google Scholar 

  • Shram MJ, Funk D, Li Z, Lê AD (2007) Nicotine self-administration, extinction and reinstatement in adolescent and adult male rats: evidence against a biological vulnerability to nicotine addiction during adolescence. Neuropsychopharmacology (in press)

  • Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463

    Article  PubMed  CAS  Google Scholar 

  • Stansfield KH, Kirstein CL (2006) Effects of novelty on behavior in the adolescent and adult rat. Dev Psychobiol 48:10–15

    Article  PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2003) Overview of findings from the 2003 National Survey on Drug Use and Health. Department of Health and Human Services, pp 14–21

  • Suto N, Austin JD, Vezina P (2001) Locomotor response to novelty predicts a rat’s propensity to self-administer nicotine. Psychopharmacology (Berl) 158:175–180

    Article  CAS  Google Scholar 

  • Teicher MH, Barber NI, Gelbard HA, Gallitano AL, Campbell A, Marsh E, Baldessarini RJ (1993) Developmental differences in acute nigrostriatal and mesocorticolimbic system response to haloperidol. Neuropsychopharmacology 9:147–156

    PubMed  CAS  Google Scholar 

  • Torrella TA, Badanich KA, Philpot RM, Kirstein CL, Wecker L (2004) Developmental differences in nicotine place conditioning. Ann N Y Acad Sci 1021:399–403

    Article  PubMed  CAS  Google Scholar 

  • Trauth JA, Seidler FJ, McCook EC, Slotkin TA (1999) Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Res 851:9–19

    Article  PubMed  CAS  Google Scholar 

  • Vann RE, Balster RL, Beardsley PM (2006) Dose, duration, and pattern of nicotine administration as determinants of behavioral dependence in rats. Psychopharmacology (Berl) 184:482–493

    Article  CAS  Google Scholar 

  • Vastola BJ, Douglas LA, Varlinskaya EI, Spear LP (2002) Nicotine-induced conditioned place preference in adolescent and adult rats. Physiol Behav 77:107–114

    Article  PubMed  CAS  Google Scholar 

  • Watkins SS, Epping-Jordan MP, Koob GF, Markou A (1999) Blockade of nicotine self-administration with nicotinic antagonists in rats. Pharmacol Biochem Behav 62:743–751

    Article  PubMed  CAS  Google Scholar 

  • Wiley JL, O’Connell MM, Tokarz ME, Wright MJ Jr (2007) Pharmacological effects of acute and repeated administration of Delta(9)-tetrahydrocannabinol in adolescent and adult rats. J Pharmacol Exp Ther 320:1097–1105

    Article  PubMed  CAS  Google Scholar 

  • Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225

    Article  PubMed  CAS  Google Scholar 

  • Yokel RA, Wise RA (1975) Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549

    Article  PubMed  CAS  Google Scholar 

  • Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, Ishii H, Tanaka M (1993) Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid agonist and nicotine as examined with in vivo microdialysis. Brain Res 624:277–280

    Article  PubMed  CAS  Google Scholar 

  • Zuckerman M (1994) Behavioral expressions and biosocial bases of sensation seeking. Cambridge University Press, New York

    Google Scholar 

Download references

Acknowledgements

This work was supported by CAMH. MJS was supported by a Natural Sciences and Engineering Research Council postgraduate scholarship and a Canadian Institute for Health Research Strategic Training Programme in Tobacco Research fellowship. MJS completed this work at CAMH as part of her doctoral thesis and is currently at DecisionLine Clinical Research Corporation, Toronto, Canada.

Conflict of interest statement

We declare that no financial support or compensation has been received from any individual or corporate entity over the past 2 years for research or professional services, and there are no personal financial holdings that may be perceived as constituting a potential conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Megan J. Shram.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shram, M.J., Li, Z. & Lê, A.D. Age differences in the spontaneous acquisition of nicotine self-administration in male Wistar and Long–Evans rats. Psychopharmacology 197, 45–58 (2008). https://doi.org/10.1007/s00213-007-1003-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-1003-9

Keywords

Navigation