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Self-administered and noncontingent nicotine enhance reinforced operant responding in rats: impact of nicotine dose and reinforcement schedule

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Abstract

Rationale

Nicotine infusions that are self-administered (contingent) or response-independent (noncontingent) increase lever pressing for a reinforcing nonpharmacological stimulus in rats, suggesting that in addition to primary reinforcement, nicotine self-administration may result from nicotine enhancing the reinforcement derived from nonnicotine stimuli.

Objectives

Based on our previous research, in this study, we tested the hypothesis that contingent and noncontingent nicotine would equally elevate responding for a moderately reinforcing visual stimulus, across a range of nicotine doses on both fixed ratio and progressive ratio reinforcement schedules.

Materials and methods

The rats lever pressed for a visual stimulus with contingent nicotine, noncontingent nicotine, or contingent saline. Separate groups responded for saline or nicotine without the visual stimulus. Three doses of nicotine (0.01, 0.03, and 0.09 mg/kg per infusion, free base) were tested in a between-groups design. After responding on an escalating fixed ratio reinforcement schedule, the rats were tested on a progressive ratio schedule.

Results

Compared to responding for the visual stimulus with saline, both contingent and noncontingent nicotine equally elevated lever pressing for the stimulus at each dose on fixed and progressive ratio schedules. In the absence of the stimulus, only the highest nicotine dose sustained self-administration.

Conclusions

The ability of noncontingent nicotine to elevate responding for a moderately reinforcing visual stimulus occurs across a range of doses, and both self-administered and noncontingent nicotine equally increase motivation to obtain the stimulus, as reflected by performance on a progressive ratio schedule. In the absence of a contingent stimulus, primary reinforcement from nicotine only supports self-administration at high nicotine doses in rats.

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References

  • Addy NA, Nakijama A, Levin ED (2003) Nicotinic mechanisms of memory: effects of acute local DHbetaE and MLA infusions in the basolateral amygdala. Brain Res Cogn Brain Res 16:51–57

    Article  PubMed  CAS  Google Scholar 

  • Barr AM, Phillips AG (1999) Withdrawal following repeated exposure to d-amphetamine decreases responding for a sucrose solution as measured by a progressive ratio schedule of reinforcement. Psychopharmacology (Berl) 141:99–106

    Article  CAS  Google Scholar 

  • Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2002a) Environmental stimuli promote the acquisition of nicotine self-administration in rats. Psychopharmacology (Berl) 163:230–237

    Article  CAS  Google Scholar 

  • Caggiula AR, Donny EC, Chaudhri N, Perkins KA, Evans-Martin FF, Sved AF (2002b) Importance of nonpharmacological factors in nicotine self-administration. Physiol Behav 77:683–687

    Article  PubMed  CAS  Google Scholar 

  • Chaudhri N (2005) Complex interactions between nicotine and nonpharmacological stimuli reveal a novel role for nicotine in reinforcement. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA

  • Chaudhri N, Caggiula AR, Donny EC, Booth S, Gharib MA, Craven LA, Allen SS, Sved AF, Perkins KA (2005) Sex differences in the contribution of nicotine and nonpharmacological stimuli to nicotine self-administration in rats. Psychopharmacology (Berl) 180:258–266

    Article  CAS  Google Scholar 

  • Chaudhri N, Caggiula AR, Donny EC, Palmatier MI, Liu X, Sved AF (2006) Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement. Psychopharmacology (Berl) 184:353–366

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  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 

  • Dani JA, De Biasi M (2001) Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 70:439–446

    Article  PubMed  CAS  Google Scholar 

  • Dani JA, Ji D, Zhou FM (2001) Synaptic plasticity and nicotine addiction. Neuron 31:349–352

    Article  PubMed  CAS  Google Scholar 

  • Depoortere RY, Li DH, Lane JD, Emmett-Oglesby MW (1993) Parameters of self-administration of cocaine in rats under a progressive-ratio schedule. Pharmacol Biochem Behav 45:539–548

    Article  PubMed  CAS  Google Scholar 

  • 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 (Berl) 136:83–90

    Article  CAS  Google Scholar 

  • Donny EC, Caggiula AR, Mielke MM, Booth S, Gharib MA, Hoffman A, Maldovan V, Shupenko C, McCallum SE (1999) Nicotine self-administration in rats on a progressive ratio schedule of reinforcement. Psychopharmacology (Berl) 147:135–142

    Article  CAS  Google Scholar 

  • 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 (Berl) 151:392–405

    Article  CAS  Google Scholar 

  • 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 (Berl) 169:68–76

    Article  CAS  Google Scholar 

  • Grillner P, Svensson TH (2000) Nicotine-induced excitation of midbrain dopamine neurons in vitro involves ionotropic glutamate receptor activation. Synapse 38:1–9

    Article  PubMed  CAS  Google Scholar 

  • Grilly DM, Simon BB, Levin ED (2000) Nicotine enhances stimulus detection performance of middle-and old-aged rats: a longitudinal study. Pharmacol Biochem Behav 65:665–670

    Article  PubMed  CAS  Google Scholar 

  • Jones IW, Wonnacott S (2004) Precise localization of alpha7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area. J Neurosci 24:11244–11252

    Article  PubMed  CAS  Google Scholar 

  • Lehman RS (1995) Statistics in the behavioral sciences. A conceptual approach. Brooks/Cole

  • Levin ED (2002) Nicotinic receptor subtypes and cognitive function. J Neurobiol 53:633–640

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Caggiula AR, Palmatier MI, Donny EC, Chaudhri N, Sved AF (2005) Reinforcement-enhancing effect of nicotine depends on the reinforcement valence of nondrug stimulus. Society for Neuroscience abstract 1027.14

  • Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27:349–357

    Article  PubMed  CAS  Google Scholar 

  • Mansvelder HD, McGehee DS (2002) Cellular and synaptic mechanisms of nicotine addiction. J Neurobiol 53:606–617

    Article  PubMed  CAS  Google Scholar 

  • Mansvelder HD, Keath JR, McGehee DS (2002) Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 33:905–919

    Article  PubMed  CAS  Google Scholar 

  • Mansvelder HD, De Rover M, McGehee DS, Brussaard AB (2003) Cholinergic modulation of dopaminergic reward areas: upstream and downstream targets of nicotine addiction. Eur J Pharmacol 480:117–123

    Article  PubMed  CAS  Google Scholar 

  • Markou A, Weiss F, Gold LH, Caine SB, Schulteis G, Koob GF (1993) Animal models of drug craving. Psychopharmacology (Berl) 112:163–182

    Article  CAS  Google Scholar 

  • Matteson GL, Palmatier MI, Liu X, Chaudhri N, Caggiula AR, Donny EC, Sved AF (2006) The reinforcement enhancing effect of nicotine depends on the incentive value of a nonpharmacological reinforcer. The 12th annual meeting of the Society for Research on Nicotine and Tobacco, Orlando, FL, February 15–18

  • Nicola SM, Deadwyler SA (2000) Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the timing of cocaine-seeking behavior in rats on a progressive ratio schedule of reinforcement. J Neurosci 20:5526–5537

    PubMed  CAS  Google Scholar 

  • Olausson P, Jentsch JD, Taylor JR (2004) Nicotine enhances responding with conditioned reinforcement. Psychopharmacology (Berl) 171:173–178

    Article  CAS  Google Scholar 

  • Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, Donny E, Liu X, Booth S, Gharib MA, Craven LA, 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 (Berl) 184:391–400

    Article  CAS  Google Scholar 

  • Phillips AG, Fibiger HC (1990) Role of reward and enhancement of conditioned reward in persistence of responding for cocaine. Behav Pharmacol 1:269–282

    PubMed  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 

  • Rasmussen T, Swedberg MD (1998) Reinforcing effects of nicotinic compounds: intravenous self-administration in drug-naive mice. Pharmacol Biochem Behav 60:567–573

    Article  PubMed  CAS  Google Scholar 

  • Rezvani AH, Bushnell PJ, Levin ED (2002) Effects of nicotine and mecamylamine on choice accuracy in an operant visual signal detection task in female rats. Psychopharmacology (Berl) 164:369–375

    Article  CAS  Google Scholar 

  • Rice ME, Cragg SJ (2004) Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci 7:583–584

    Article  PubMed  CAS  Google Scholar 

  • Risner ME, Goldberg SR (1983) A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion. J Pharmacol Exp Ther 224:319–326

    PubMed  CAS  Google Scholar 

  • Robbins TW, Cador M, Taylor JR, Everitt BJ (1989) Limbic–striatal interactions in reward-related processes. Neurosci Biobehav Rev 13:155–162

    Article  PubMed  CAS  Google Scholar 

  • Robbins TW (1976) Relationship between reward-enhancing and stereotypical effects of psychomotor stimulant drugs. Nature 264:57–59

    Article  PubMed  CAS  Google Scholar 

  • Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609

    Article  PubMed  CAS  Google Scholar 

  • Schilstrom B, Nomikos GG, Nisell M, Hertel P, Svensson TH (1998) N-Methyl-d-aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens. Neuroscience 82:781–789

    Article  PubMed  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 

  • Silva AJ (2003) Molecular and cellular cognitive studies of the role of synaptic plasticity in memory. J Neurobiol 54:224–237

    Article  PubMed  CAS  Google Scholar 

  • Stafford D, LeSage MG, Glowa JR (1998) Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review. Psychopharmacology (Berl) 139:169–184

    Article  CAS  Google Scholar 

  • Stewart J (1960) Reinforcing effects of light as a function of intensity and reinforcement schedule. J Comp Physiol Psychol 53:187–193

    Article  PubMed  CAS  Google Scholar 

  • Stolerman IP, Mirza NR, Hahn B, Shoaib M (2000) Nicotine in an animal model of attention. Eur J Pharmacol 393:147–154

    Article  PubMed  CAS  Google Scholar 

  • Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl) 84:405–412

    Article  CAS  Google Scholar 

  • Terry AV, Jr., Risbrough VB, Buccafusco JJ, Menzaghi F (2002) Effects of (+/−)-4-[[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a selective ligand for nicotinic acetylcholine receptors, in tests of visual attention and distractibility in rats and monkeys. J Pharmacol Exp Ther 301:284–292

    Article  PubMed  CAS  Google Scholar 

  • USDHHS (1988) Nicotine addiction: a report of the surgeon general. US Department of Health and Human Services, Office of the Assistant Secretary for Health, Office on Smoking and Health, Rockville, MD

  • Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

“Principles of laboratory animal care” (NIH No. 85-23, revised 1985) were followed throughout all experiments. The University of Pittsburgh Institutional Animal Care and Use Committee assurance number A3187-01 approved this research. The preparation of this manuscript was supported by National Institute on Drug Abuse research grants DA-010464 and DA-012655 and by a Howard Hughes pre-doctoral research fellowship awarded to N. Chaudhri.

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Authors and Affiliations

  1. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Nadia Chaudhri, Matthew I. Palmatier & Alan F. Sved

  2. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA

    Anthony R. Caggiula, Eric C. Donny, Sheri Booth, Maysa Gharib, Laure Craven, Matthew I. Palmatier & Xiu Liu

  3. Ernest Gallo Clinic and Research Center, University of California at San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA, 94608, USA

    Nadia Chaudhri

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  1. Nadia Chaudhri
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  2. Anthony R. Caggiula
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Correspondence to Nadia Chaudhri.

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Chaudhri, N., Caggiula, A.R., Donny, E.C. et al. Self-administered and noncontingent nicotine enhance reinforced operant responding in rats: impact of nicotine dose and reinforcement schedule. Psychopharmacology 190, 353–362 (2007). https://doi.org/10.1007/s00213-006-0454-8

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