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Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone

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Abstract

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 μg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 μg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

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References

  • Altshuler HL, Phillips PE, Feinhandler DA (1980) Alteration of ethanol self-administration by naltrexone. Life Sci 26:679–688

    Article  PubMed  CAS  Google Scholar 

  • Ando K (1975) Profile of drug effects on temporally spaced responding in rats. Pharmacol Biochem Behav 3:833–841

    Article  PubMed  CAS  Google Scholar 

  • Bovet D, Bovet-Nitti F (1965) Action of nicotine on conditioned behavior in naive and pretrained rats. In: von Euler US (ed) Tobacco alkaloids and related compounds. Pergamon, Oxford, pp 125–143

    Google Scholar 

  • Clarke MSG (1969) Self-administrated nicotine solutions preferred to placebo by the rat. Br J Pharmacol 35:376

    Google Scholar 

  • Davis TR, Kensler CJ, Dews PB (1973) Comparison of behavioral effects of nicotine, d-amphetamine, caffeine, and dimethylheptyl tetrahydrocannabinol in squirrel monkeys. Psychopharmacologia 32:51–65

    Article  PubMed  CAS  Google Scholar 

  • DeNoble VJ, Svikis DS, Meisch RA (1981) Orally delivered pentobarbital as a reinforcer for rhesus monkeys with concurrent access to water: effects of concentration, fixed-ratio size and liquid positions. Pharmacol Biochem Behav 16:113–117

    Article  Google Scholar 

  • DeNoble VJ, Dragan YP, Carron L (1982a) Behavioral effects of intraventricularly administered (−)-nicotine on fixed-ratio schedules of food presentation in rats. Psychopharmacology 77:317–321

    Article  PubMed  CAS  Google Scholar 

  • DeNoble VJ, Ryan FJ, Dragan YP, Mele PC, Naworal J, Kornfeld R (1982b) Antagonism of chronic nicotine administration: effects on schedule-controlled behavior in rats. Soc Neurosci Abstr 8:109

    Google Scholar 

  • Falk JL, Samson MH (1975) Schedule-induced physical dependence on ethanol. Pharmacol Rev 27:44–464

    Google Scholar 

  • Goldberg SR (1973) Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection or d-amphetamine injection in the squirrel monkey. J Pharmacol Exp Ther 186:18–30

    PubMed  CAS  Google Scholar 

  • Goldberg SR, Spealman RD (1983) Suppression of behavior by intravenous injections of nicotine or by electric shock in squirrel monkeys: effects of chlordiazexpoxide and mecamylamine. J Pharmacol Exp Ther 224:334–340

    PubMed  CAS  Google Scholar 

  • Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575

    Article  PubMed  CAS  Google Scholar 

  • Griffiths PR, Brady JV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology. Academic, New York, pp 163–208

    Google Scholar 

  • Hanson HM, Ivester CA, Morton BR (1979) Nicotine self-administration in rats. In: Krasnegor NA (ed) Cigarette smoking as a dependence process. Government Printing Office, Washington DC, pp 70–90

    Google Scholar 

  • Hirschhorn ID, Rosecrans JA (1974) Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effects of nicotine. Psychopharmacologia 40:109–120

    Article  PubMed  CAS  Google Scholar 

  • Holzman SG (1974) Behavioral effects of separate and combined administration of naloxone and d-amphetamine. J Pharmacol Exp Ther 189:51–60

    PubMed  Google Scholar 

  • Karras A, Kane JM (1980) Naloxone reduces cigarette smoking. Life Sci 27:1541–1545

    Article  PubMed  CAS  Google Scholar 

  • Lang WJ, Latiff AA, Mcqueen A, Singer G (1977) Self-administration of nicotine with and without a food delivery schedule. Pharmacol Biochem Behav 7:65–70

    Article  PubMed  CAS  Google Scholar 

  • Latiff AA, Smith LA, Lang WJ (1980) Effects of changing dosage and urinary pH in rats self-administering nicotine on a food delivery schedule. Pharmacol Biochem Behav 13:209–213

    Article  PubMed  CAS  Google Scholar 

  • Leander JD, Hart JC, Lochner MA, Hynes MD III, Zimmerman DM (1982) Novel phenylpiperidine opioid antagonists and partial agonists: effects on fluid consumption. Eur J Pharmacol 81:185–192

    Article  PubMed  CAS  Google Scholar 

  • Margules DL, Moisset B, Lewis MJ, Shibuya H, Pert CB (1978) β-Endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa). Science 202:988–991

    Article  PubMed  CAS  Google Scholar 

  • McIssac RJ (1962) The relationship between distribution and pharmacological activity of hexamethonium-N-methyl C-14. J Pharmacol Exp Ther 135:335–343

    Google Scholar 

  • Meltzer LT, Rosecrans JA, Aceto MD, Harris LS (1980) Discriminative stimulus properties of the optical isomers of nicotine. Psychopharmacology 68:283–286

    Article  PubMed  CAS  Google Scholar 

  • Morrison CF (1967) A comparison of the effects of nicotine and amphetamine on DRL performance in the rat. Psychopharmacologia 12:176–180

    Article  Google Scholar 

  • Morrison CF, Stephenson JA (1969) Nicotine injections as the conditioned stimulus in discrimination learning. Psychopharmacologia 15:351–360

    Article  PubMed  CAS  Google Scholar 

  • Morrison CF, Goodyear JM, Sellers CM (1969) Antagonism by antimuscarinic and ganglion-blocking drugs of some of the behavioural effects of nicotine. Psychopharmacologia 15:341–350

    Article  PubMed  CAS  Google Scholar 

  • Pickens R, Meisch RA, Thompson T (1978) Drug self-administration. In: Iverson LL, Iverson SD, Snyder SH (eds) Handbook of psychopharmacology, vol 12. Plenum, New York, pp 1–37

    Google Scholar 

  • Pradhan SN (1970) Effects of nicotine on several schedules of behavior in rats. Arch Int Pharmacodyn Ther 183:127–138

    PubMed  CAS  Google Scholar 

  • Pradhan SN, Dutta SN (1970) Comparative effects of nicotine and amphetamine on timing behavior in rats. Neuropharmacology 9:9–16

    Article  PubMed  CAS  Google Scholar 

  • Reynolds RW (1958) The relationship between stimulation voltage and rate of hypothalamic self-stimulation in the rat. J Comp Physiol Psychol 51:193–198

    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 

  • Romer D, Buscher H, Hill RC, Maurer R, Petcher TJ, Welle HB, Bakel HC, Akkerman AM (1981) A potent, long acting opiate kappa agonist. Life Sci 27:1209–1213

    Google Scholar 

  • Sahley TL, Bernston GG (1979) Antinociceptive effects of central and systemic administration of nicotine in the rat. Psychopharmacology 65:279–283

    Article  PubMed  CAS  Google Scholar 

  • Schechter MC, Rosecrans JA (1972) Effects of mecamylamine on discrimination between nicotine and arecoline produced cues. Euro J Pharmacol 17:179–182

    Article  CAS  Google Scholar 

  • Segal DS, Browne RG, Arnsten A, Derrington DC, Bloom FE, Davis AV, Guillemin R, Ling N (1979) Characteristics of β-endorphin-induced behavioral activation and immobilization. In: Usdin E, Bunney WE, Kline NS (eds) Endorphins in mental health research. Oxford University Press, New York, pp 307–324

    Google Scholar 

  • Singer G, Simpson F, Lang WJ (1978) Schedule-induced self-injections of nicotine with recovered body weight. Pharmacol Biochem Behav 9:387–389

    Article  PubMed  CAS  Google Scholar 

  • Smith LA, Lang WJ (1980) Changes occurring in self-administration of nicotine by rats over a 28 day period. Pharmacol Biochem Behav 13:215–220

    Article  PubMed  CAS  Google Scholar 

  • Spealman RD, Goldberg SR (1982) Maintenance of schedule-controlled behavior by intravenous injections of nicotine in squirrel monkeys. J Pharmacol Exp Ther 223:402–408

    PubMed  CAS  Google Scholar 

  • Stein L, Belluzzi JD (1979) Brain endorphins: possible mediators of pleasurable states. In: Usdin E, Bunney WE, Kline NS (eds) Endorphins in mental health research. Oxford University Press, New York, pp 375–389

    Google Scholar 

  • Stitzer M, Morrison J, Domino EF (1970) Effects of nicotine on fixed-internal behavior and their modification by cholinergic antagonists. J Pharmacol Exp Ther 171:165–177

    Google Scholar 

  • Weeks JR (1972) Long-term intravenous infusion. In: Myers RD (ed) Methods in psychobiology, vol 2. Academic, New York, pp 155–167

    Google Scholar 

Download references

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Correspondence to Victor J. DeNoble or Paul C. Mele.

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Editor's Note: This manuscript was originally submitted, edited and accepted for publication in 1986. Herbert Barry III who served as coordinating and field editor during this period recounts the events surrounding this manuscript and related manuscripts in his commentary "Censorship by a Tobacco Company", Psychopharmacology DOI 10.1007/s00213-005-0061-0.

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DeNoble, V.J., Mele, P.C. Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone. Psychopharmacology 184, 266–272 (2006). https://doi.org/10.1007/s00213-005-0054-z

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  • DOI: https://doi.org/10.1007/s00213-005-0054-z

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