Abstract
Rationale
Nicotine is widely assumed to convey reinforcing properties upon tobacco-related stimuli through associative learning. We have proposed that the reinforcement derived from these conditional stimuli can be inflated by a nonassociative “reinforcement-enhancing” effect of nicotine.
Objectives
Experiment 1 investigated whether nicotine could establish a stimulus as a conditioned reinforcer. Using the same subjects, Experiment 2 examined whether responding for a nicotine-associated stimulus was enhanced by response-independent administration of nicotine.
Materials and methods
Self-administered nicotine (Paired group, 0.03 mg kg1 infusion−1) or saline (conditional stimulus or CS-Only group) was paired with a stimulus light (CS). An Unpaired group, yoked to the Paired group, received equal exposure to nicotine and the CS, but each event was temporally separated. To test for conditioning, the CS was then made contingent upon a novel lever-pressing response. In Experiment 2, a subset of the paired rats (self-administering) continued to lever press while receiving contingent nicotine and the CS. To determine whether nicotine enhanced responding for the CS, two remaining subsets of the Paired group responded for the CS while receiving nicotine (YNIC) or saline (YSAL) yoked to the self-administering rats. All remaining control groups received response-contingent CS presentations, together with yoked nicotine or saline.
Results
Pairing self-administered nicotine with the CS promoted the acquisition of a novel response for the CS. In Experiment 2, the Paired YNIC group responded at higher rates than control groups receiving YNIC or YSAL.
Conclusions
Nicotine can establish stimuli as conditioned reinforcers for which noncontingent nicotine can enhance responding.
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References
Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco dependence. Curr Drug Targets CNS Neurol Disord 1:413–421
Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward. Psychopharmacology 153:31–43
Bevins RA (2005) The reference-dose place conditioning procedure yields a graded dose-effect function. Int J Comp Psychol 18:101–111
Butler RA, Harlow HF (1957) Discrimination learning and learning sets to visual exploration incentives. J Gen Psych 57:257–264 (Heldref Publications)
Caggiula AR, Donny EC, White AR, Chaudhri N, Gharib M, Booth S, Sved AF (2001) Non-contingent nicotine enhances responding maintained by behaviorally contingent environmental cues. Society for Neuroscience Meetings, San Diego (Abstr)
Chaudhri N, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, Palmatier MI, Liu X, Sved AF (2006a) Operant responding for conditioned and unconditioned reinforcers in rats is differentially enhanced by the primary reinforcing and reinforcement-enhancing effects of nicotine. Psychopharmacology 189:27–36
Chaudhri N, Caggiula AR, Donny EC, Palmatier MI, Liu X, Sved AF (2006b) Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement. Psychopharmacology 184:353–366
Chaudhri N, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, Palmatier MI, Liu X, Sved AF (2007) Self-administered and noncontingent nicotine enhance reinforced operant responding in rats: impact of nicotine dose and reinforcement schedule. Psychopharmacology 190:353–362
Chiamulera C (2005) Cue reactivity in nicotine and tobacco dependence: a “multiple-action” model of nicotine as a primary reinforcement and as an enhancer of the effects of smoking-associated stimuli. Brain Res Brain Res Rev 48:74–97
Cohen C, Perrault G, Griebel G, Soubrie P (2005) Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: reversal by the cannabinoid (CB1) receptor antagonist, rimonabant (SR141716). Neuropsychopharmacology 30:145–155
Conklin CA, Tiffany ST (2002) Applying extinction research and theory to cue-exposure addiction treatments. Addiction 97:155–167
Di Chiara G (2000) Behavioural pharmacology and neurobiology of nicotine rewrd and dependence. In: Clementi F, Fomasari D, Gotti C (eds) Handbook of experimental pharmacology: neuronal nicotinic receptors. Springer, Berlin
Di Ciano P, Everitt BJ (2004) Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: implications for the persistence of addictive behaviour. Neuropharmacology 47(Suppl 1):202–213
Donny EC, Caggiula AR, Knopf S, Brown C (1995) Nicotine self-administration in rats. Psychopharmacology 122:390–394
Donny EC, Caggiula AR, Mielke MM, Jacobs KS, Rose C, Sved AF (1998) Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency. Psychopharmacology 136:83–90
Donny EC, Caggiula AR, Rowell PP, Gharib MA, Maldovan V, Booth S, Mielke MM, Hoffman A, McCallum S (2000) Nicotine self-administration in rats: estrous cycle effects, sex differences and nicotinic receptor binding. Psychopharmacology 151:392–405
Donny EC, Chaudhri N, Caggiula AR, Evans-Martin FF, Booth S, Gharib MA, Clements LA, Sved AF (2003) Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement. Psychopharmacology 169:68–76
Donny EC, Houtsmuller E, Stitzer ML (2007) Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction 102:324–334
Fowler H (1971) Implications of sensory reinforcement. In: Glaser R (ed) The nature of reinforcement. A symposium of the learning research and development center, University of Pittsburgh. Academic, New York, pp 151–195
Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575
Kruzich PJ, Congleton KM, See RE (2001) Conditioned reinstatement of drug-seeking behavior with a discrete compound stimulus classically conditioned with intravenous cocaine. Behav Neurosci 115:1086–1092
Lazev AB, Herzog TA, Brandon TH (1999) Classical conditioning of environmental cues to cigarette smoking. Exp Clin Psychopharmacol 7:56–63
Le Foll B, Goldberg SR (2005) Nicotine induces conditioned place preferences over a large range of doses in rats. Psychopharmacology 178:481–492
Liu X, Palmatier MI, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, Sved AF (2007) Cholinergic substrates of the reinforcement enhancing effects of nicotine. Psychopharmacology (in press). DOI 10.1007/s00213-007-0863-3
Mackintosh NJ (1974) The psychology of animal learning. Academic, New York
Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, Donny EC, Liu X, Booth S, Gharib M, Craven L, Sved AF (2006) Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers. Psychopharmacology 184:391–400
Palmatier MI, Liu X, Caggiula AR, Donny EC, Sved AF (2007a) The role of nicotinic acetylcholine receptors in the primary reinforcing and reinforcement-enhancing effects of nicotine. Neuropsychopharmacology 32:1098–1108
Palmatier MI, Matteson GL, Black JJ, Liu X, Caggiula AR, Craven L, Donny EC, Sved AF (2007b) The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections. Drug Alcohol Depend 89(1):52–59
Payne TJ, Schare ML, Levis DJ, Colletti G (1991) Exposure to smoking-relevant cues: effects on desire to smoke and topographical components of smoking behavior. Addict Behav 16:467–479
Robbins TW (1976) Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs. Nature 264:57–59
Rose JE (2006) Nicotine and nonnicotine factors in cigarette addiction. Psychopharmacology 184:274–285
Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609
Shoaib M, Stolerman IP, Kumar RC (1994) Nicotine-induced place preferences following prior nicotine exposure in rats. Psychopharmacology 113:445–452
Stewart J (1960) Reinforcing effects of light as a function of intensity and reinforcement schedule. J Comp Physiol Psychol 53:187–193
Stewart J, Hurwitz H (1958) Studies in light-reinforced behaviour: III. The effect of continuous, zero and fixed-ratio reinforcement. Q J Exp Psychol 10:56–61
Taylor JR, Jentsch JD (2001) Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine (“Ecstasy”). Biol Psychiatry 50:137–143
Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology 84:405–412
US Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction: a report of the surgeon general. Center for Health Promotion and Education. Office on Smoking and Health United States. Public Health Service. Office of the Surgeon General DHHS Publication No. (CDC) 88-8406
Acknowledgment
We thank Sheri Booth, Maysa Gharib, and Laure Craven for their assistance in conducting the studies. All experiments followed the “Principles of laboratory animal care” (NIH #85-23, revised 1985) and were approved by the University of Pittsburgh Institutional Animal Care and Use Committee (Assurance # A3187-01). This research was supported by NIH grants DA-10464, DA-19278, and DA-17288.
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Palmatier, M.I., Liu, X., Matteson, G.L. et al. Conditioned reinforcement in rats established with self-administered nicotine and enhanced by noncontingent nicotine. Psychopharmacology 195, 235–243 (2007). https://doi.org/10.1007/s00213-007-0897-6
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DOI: https://doi.org/10.1007/s00213-007-0897-6