Abstract
Rats were trained to discriminate nicotine (0.4 mg/kg SC) from saline in a standard two-bar operant conditioning procedure with food reinforcement. The response to nicotine was dose-related and at the ED50 of 0.14 mg/kg, plasma nicotine concentrations were similar to those reported previously for cigarette smokers who inhale. The nicotine analogues anabasine and cytisine increased nicotine-appropriate responding in a dose-related manner. Animals predominantly responded on the saline-associated lever when administered drugs from a range of pharmacological classes, even at doses that were sufficiently large to reduce the overall numbers of responses. The results confirm that the nicotine discriminative stimulus is highly specific. Previous work has shown anabasine and cytisine to be active at nicotinic-cholinergic binding sites in rat brain. The finding that there is some correlation between the behavioural effects of these compounds and their actions at the nicotine binding site may indicate that the nicotine cue is mediated throuth a cholinergic receptor.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Abood LG, Lowy K, Tometsko A, Booth H (1978) Electrophysiological, behavioural, and chemical evidence for a non-cholinergic stereospecific site for nicotine in rat brain. J Neurosci Res 3:327–333
Barlow RB, McLeod LJ (1969) Some studies on cytisine and its methylated derivatives. Br J Pharmacol 35:161–174
Barry H III (1974) Classification of drugs according to their discriminable effects in rats. Fed Proc 33:1814–1824
Chance WT, Murfin D, Krynock GM, Rosecrans JA (1977) A description of the nicotine stimulus and tests of its generalization to amphetamine. Psychopharmacology 55:19–26
Colpaert FC (1977) Drug-produced cues and states: Some theoretical and methodological inferences. In: Lal H (ed) Discriminative stimulus properties of drugs. Plenum, New York, pp 5–21
D'Mello GD, Stolerman IP (1977) Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats. Br J Pharmacol 61:415–422
Feyerabend C, Russell MA (1980) Assay of nicotine in biological materials: sources of contamination and their elimination. J Pharm Pharmacol 32:178–181
Garcha HS, Giardini V, Pratt JA, Stolerman IP (1983) Anabasine and cytisine: nicotine-like behavioural effecs in a drug-discrimination procedure. Br J Pharmacol 79:272P
Garcha HS, Kumar R, Pratt JA, Stolerman IP (1982) Characteristics of the nicotine cue in rats. Br J Pharmacol 76:227P
Gilbert DG (1979) Paradoxical tranquilizing and emotion-reducing effects of nicotine. Psychol Bull 86:643–661
Giorguieff MF, Le Floc'h ML, Glowinski J, Besson MJ (1977) Involvement of cholinergic presynaptic receptors of nicotinic and muscarinic types in the control of the spontaneous release of dopamine from striatal dopaminergic terminals in the rat. J Pharmacol Exp Ther 200:535–544
Guidotti A, Toffano G, Costa E (1978) An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in rat brain. Nature 275:553–555
Haefely W (1974) The effects of various “nicotine-like” agents in the cat superior cervical ganglion in situ. Naunyn-Schmiedeberg's Arch Pharmacol 281:93–117
Haefely W, Kulcsar A, Möhler H, Pieri L, Polc P, Schaffner R (1975) Possible involvement of GABA in the central actions of benzodiazepines. In: Costa E, Greengard P (eds) Advances in biochemical psychopharmacology, vol 14. Raven Press, New York, pp 131–151
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. Psychopharmacology 40:109–120
Ho BT, Huang J-T (1975) Role of dopamine in d-amphetamine-induced discriminative responding. Pharmacol Biochem Behav 3:1085–1092
Meltzer LT, Rosecrans JA (1981) Discriminative stimulus properties of arecoline: A new approach for studying central muscarinic receptors. Psychopharmacology 75:383–387
Morrison CF, Stephenson JA (1969) Nicotine injections as the conditioned stimulus in discrimination learning. Psychopharmacologia 15:351–360
Pieri L, Schaffner R, Scherschlicht R, Polc P, Sepinwall J, Davidson A, Möhler H, Cumin R, Da Prada M, Burkard WP, Keller HH, Müller RK, Gerold M, Pieri M, Cook L, Haefely W (1981) Pharmacology of midazolam. Drug Res 31:2180–2201
Romano C (1981) Nicotine action on rat colon. J Pharmacol Exp Ther 217:828–833
Romano C, Goldstein A (1980) Stereospecific nicotine receptors on rat brain membranes. Science 210:647–650
Romano C, Goldstein A, Jewell NP (1981) Characterization of the receptor mediating the nicotine discriminative stimulus. Psychopharmacology 74:310–315
Rosecrans JA, Chance WT (1977) Cholinergic and non-cholinergic aspects of the discriminative stimulus properties of nicotine. In: Lal H (ed) Discriminative stimulus properties of drugs. Plenum, New York, pp 155–185
Rosecrans JA, Kallman MJ, Glennon R (1978) The nicotine cue: an overview. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: Ten years of progress. Elsevier-North Holland, Amsterdam, pp 69–81
Russell MAH, Jarvis M, Iyer R, Feyerabend C (1980) Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers. Br Med J 280:972–976
Schechter MD, Rosecrans JA (1972) Nicotine as a discriminative cue in rats: Inability of related drugs to produce a nicotine-like cueing effect. Psychopharmacologia 27:379–387
Schwab LS, Kritzer MF (1982) The effect of cholinergic antagonists on a central response to nicotine. Experientia 38:119–120
Sershen H, Reith MEA, Lajtha A, Gennaro J (1981) Non-cholinergic, saturable binding of (±)-[3H]nicotine to mouse brain. Journal of Receptor Research 2:1–15
Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa University Press, Iowa
Stolerman IP, D'Mello GD (1981) Role of training conditions in discrimination of central nervous stimulants by rats. Psychopharmacology 73:295–303
Stolerman IP, Pratt JA, Garcha HS (1982) Further analysis of the nicotine cue in rats. In: Drug discrimination: applications in CNS pharmacology. Elsevier, Amsterdam, pp 203–210
Turner DM (1975) Influence of route of administration on metabolism of [14C] nicotine in four species. Xenobiotica 5:553–561
White FJ, Appel JB, Kuhn DM (1979) Discriminative stimulus properties of quipazine: direct serotonergic mediation. Neuropharmacology 18:143–151
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York
Yamamoto I, Inoki R, Iwatsubo K (1968) Penetration of nicotine-14C into several rat tissues in vivo and in vitro. Toxicol Appl Pharmacol 12:560–567
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pratt, J.A., Stolerman, I.P., Garcha, H.S. et al. Discriminative stimulus properties of nicotine: Further evidence for mediation at a cholinergic receptor. Psychopharmacology 81, 54–60 (1983). https://doi.org/10.1007/BF00439274
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00439274