Abstract
Rationale
Many people come in contact with psychoactive drugs, yet not all of them become addicts. Epidemiology shows that a late approach with cigarette smoking is associated with a lower probability to develop nicotine dependence. Exposure to nicotine during periadolescence, but not similar exposure in the postadolescent period, increases nicotine self-administration in rats, but underlying mechanisms remain poorly understood.
Objective
We investigated whether exposure to nicotine during or after adolescence would alter rewarding properties of the same drug at adulthood, as assessed by place conditioning.
Materials and methods
Periadolescent (PND 34–43) or postadolescent (PND 60–69) rats were injected with saline or nicotine (0.4 mg kg−1) for 10 days. The rats received three pairings with saline and three pairings with nicotine (0, 0.3, or 0.6 mg kg−1) 5 weeks after pretreatment. The rats were then tested for place conditioning in a drug-free state.
Results
Upon first exposure to the apparatus, animals pretreated with nicotine during adolescence showed elevated novelty-induced activation. The 0.3 (but not the 0.6) mg kg−1 dose failed to produce both ongoing locomotor sensitization and place conditioning in animals pretreated with nicotine following adolescence. This suggests a rightward shift in the dose–response curve, namely, a reduced efficacy of nicotine. Conversely, the same dose was effective in saline-pretreated controls and noteworthy in rats pretreated during adolescence.
Conclusion
Exposure following the adolescent period might diminish the risk to develop nicotine dependence. As for human implications, findings are consistent with a reduced vulnerability to nicotine addiction in people who start smoking late in their life.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abreu-Villaca Y, Seidler FJ, Qiao D, Tate CA, Cousins MM, Thillai I, Slotkin TA (2003) Short-term adolescent nicotine exposure has immediate and persistent effects on cholinergic systems: critical periods, patterns of exposure, dose thresholds. Neuropsychopharmacology 28:1935–1949
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
Adriani W, Spijker S, Deroche-Gamonet V, Laviola G, Le Moal M, Smit AB, Piazza PV (2003) Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats. J Neurosci 23:4712–4716
Adriani W, Granstrem O, Macri S, Izykenova G, Dambinova S, Laviola G (2004) Behavioral and neurochemical vulnerability during adolescence in mice: studies with spontaneous consumption or imposed administration of nicotine. Neuropsychopharmacology 29:869–878
Anthony JC, Petronis KR (1995) Early-onset drug use and risk of later drug problems. Drug Alcohol Depend 40:9–15
Balfour DJK, Benwell MEM, Birrell CE, Kelly RJ, Al-Aloul M (1998) Sensitization of the mesoaccumbens dopamine response to nicotine. Pharmacol Biochem Behav 59:1021–1030
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
Benwell MEM, Balfour DJK (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856
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
Breslau N, Fenn N, Peterson EL (1993) Early smoking initiation and nicotine dependence in a cohort of young adults. Drug Alcohol Depend 33:129–137
Cabib S, Puglisi-Allegra S, Genua C, Simon H, Le Moal M, Piazza PV (1996) Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus. Psychopharmacology 125:92–96
Chou SP, Pickering RP (1992) Early onset of drinking as a risk factor for lifetime alcohol-related problems. Br J Addict 87:1199–1204
Collins SL, Montano R, Izenwasser S (2004a) Nicotine treatment produces persistent increases in amphetamine-stimulated locomotor activity in periadolescent male but not female or adult male rats. Dev Brain Res 153:175–187
Collins SL, Wade D, Ledon J, Izenwasser S (2004b) Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats. Eur J Pharmacol 502:75–85
Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017
Everitt BJ, Morris KA, O'Brien A, Robbins TW (1991) The basolateral amygdala–ventral striatal system and conditioned place preference: further evidence of limbic–striatal interactions underlying reward-related processes. Neuroscience 42:1–18
Faraday MM, Elliott BM, Phillips JM, Grunberg NE (2003) Adolescent and adult male rats differ in sensitivity to nicotine's activity effects. Pharmacol Biochem Behav 74:917–931
Fuchs RA, Weber SM, Rice HJ, Neisewander JL (2002) Effects of excitotoxic lesions of the basolateral amygdala on cocaine-seeking behavior and cocaine conditioned place preference in rats. Brain Res 929:15–25
Goldberg SR, Spearman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575
Gruber E, Di Clemente RJ, Anderson MM, Lodico M (1996) Early drinking onset and its association with alcohol use and problem behavior in late adolescence. Prev Med 25:293–300
Jorenby DE, Steinpreis RE, Sherman JE, Baker TB (1990) Aversion instead of preference learning indicated by nicotine place conditioning in rats. Psychopharmacology 101:533–538
Kalivas PW, Duffy P (1990) Effects of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse 5:48–58
Kalivas PW, Duffy P (1993) Time course of extracellular dopamine and behavioral sensitization to cocaine. II. Dopamine axon terminals. J Neurosci 13:266
Kelley BM, Middaugh LD (1999) Periadolescent nicotine exposure reduced cocaine reward in adult mice. J Addict Dis 18:27–39
Laviola G, Dell'Omo G (1997) Precocious weaning and changes in social variables during pre-puberty affect cocaine reinforcing properties in adult mice. Psychobiology 25:163–170
Laviola G, Adriani W, Morley-Fletcher S, Terranova L (2002) Peculiar response of adolescent mice to acute and chronic stress and to amphetamine: evidence of sex differences. Behav Brain Res 130:117–125
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
Levin ED, Rezvani AH, Montoya D, Rose JE, Swartzwelder HS (2003) Adolescent-onset nicotine self-administration modeled in female rats. Psychopharmacology 169:141–149
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
Panagis G, Nisell M, Nomikos GG, Chergui K, Svensson TH (1996) Nicotine injections into the ventral tegmental area increase locomotion and Fos-like immunoreactivity in the nucleus accumbens of the rat. Brain Res 730:133–142
Paulson PE, Robinson TE (1995) Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats. Synapse 19:56–65
Piazza PV, Deminiere JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513
Post RM, Weiss SR, Fontana D, Pert A (1992) Conditioned sensitization to the psychomotor stimulant cocaine. Ann N Y Acad Sci 654:386–399
Reid MS, Ho LB, Berger P (1996) Effects of environmental conditioning on the development of nicotine sensitization: behavioral and neurochemical analysis. Psychopharmacology 126:301–310
Robins LN, Przybeck TR (1985) Age of onset of drug use as a factor in drug and other disorders. In: Jones CL, Battjes RL (eds) Etiology of drug abuse: implications for prevention. NIDA Res Monogr 56, pp 178–192
Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brains Res Rev 18:247–291
Rose JE, Corrigall WA (1997) Nicotine self-administration in animals and humans: similarities and differences. Psychopharmacology 30:28–40
Rose JE, Levin ED (1991) Inter-relationship between conditioned and primary reinforcement in the maintenance of cigarette smoking. In: West R, Grunberg NE (eds) British Journal of Addiction. Carfax, London, pp 605–610
Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25
Shoaib M, Stolerman IP, Kumar RC (1994) Nicotine-induced place preferences following prior nicotine exposure in rats. Psychopharmacology 113:445–452
Slotkin TA (2002) Nicotine and the adolescent brain: insights from an animal model. Neurotoxicol Teratol 24:369–384
Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463
Sutton MA, Schmidt EF, Chol KH, Schad CA, Whisler K, Simmons D, Karanlan DA, Monteggia LM, Neve RL, Self DW (2003) Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour. Nature 421:70–75
Taioli E, Wynder EL (1991) The importance of age of starting smoking. New Engl J Med 325:968–969
Tirelli E, Laviola G, Adriani W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27:163–178
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
Vanderschuren LJMJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019
Vastola BJ, Douglas LA, Varlinskaya EI, Spear LP (2002) Nicotine-induced conditioned place preference in adolescent and adult rats. Physiol Behav 77:107–114
Wilmouth CE, Spear LP (2004) Adolescent and adult rats' aversion to flavors previously paired with nicotine. Ann N Y Acad Sci 1021:462–464
Yu J, Williford WR (1992) The age of alcohol onset and alcohol, cigarette, and marijuana use patterns: an analysis of drug use progression of young adults in New York State. Int J Addict 27:1313–1323
Acknowledgements
This work was supported by "Research Studies in the Field of Addiction", Pres. Cons. Min, Italy, by NIH-USA ISS-Italy joint project, Italian Ministry of Health, by INSERM, by the University of Bordeaux 2, by I.F.R. 8, and also by a Marie Curie Fellowship to W.A. We are particularly grateful to Dr. Flavia Chiarotti for her precious help with statistics and to Giovanni Dominici for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Adriani, W., Deroche-Gamonet, V., Le Moal, M. et al. Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats. Psychopharmacology 184, 382–390 (2006). https://doi.org/10.1007/s00213-005-0125-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-0125-1