Abstract
In a standard two-lever drug discrimination paradigm, rats were trained to discriminate nicotine 0.5 mg/kg PO from saline. Injections occurred 15 min before the session. Subjects reached the training criterion in a mean of 38 sessions. Nicotine PO, SC, and IP generated similar dose-effect curves (ED50=0.073 mg/kg PO, 0.076 mg/kg SC, 0.090 mg/kg IP); the dose-effect curve for transdermal (TD) administration fell approximately 1 log unit to the right (ED50=1.34 mg/kg). The percentage of rats choosing the nicotine-appropriate lever peaked at 15 min and gradually decreased to 50% or less by 180 min for nicotine PO and TD, a time-decay function similar to that previously shown for SC administration. The nicotinic cholinergic agonist cytisine (0.5–8.0 mg/kg) PO and TD produced up to 56% nicotine-appropriate responding, while the muscarinic cholinergic agonist arecoline (1.0–4.0 mg/kg) PO and TD produced only saline-appropriate responding. The nicotine cue did not generalize to the cholinergic antagonist mecamylamine (0.125–0.5 mg/kg) PO or TD; mecamylamine 0.5 mg/kg PO but not TD completely blocked the PO and TD nicotine cues. These results show that an approximately equal cue occurs with PO, IP, and SC administration, and that the TD cue is considerably weaker. The significance of the procedure as an animal analog of human transdermal nicotine intake is discussed.
Similar content being viewed by others
References
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
Clarke PBS (1987) Nicotine and smoking: a perspective from animal studies. Psychopharmacology 92:135–143
Hendry JS, Rosecrans JA (1982) The development of pharmacological tolerance to the effect of nicotine on schedule-controlled responding in mice. Psychopharmacology 77:339–343
Hirschhorn ID, Rosecrans JA (1974) Studies on the time course and the effect of cholinergic and adrenergic receptor blockers on the stimulus effect of nicotine. Psychopharmacologia 40:109–120
Hughes JR, Pickens RW, Spring W, Keenan RM (1985) Instructions control whether nicotine will serve as a reinforcer. J Pharmacol Exp Ther 235:106–112
Jarvik ME (1973) Further observations on nicotine as the reinforcing agent in smoking. In: Dunn WL (ed) Smoking behavior: motives and incentives. Winston, Washington, DC, pp 33–50
Kallman WM, Kallman MJ, Harry GJ, Woodson PP, Rosecrans JA (1982) Nicotine as a discriminative stimulus in human subjects. In: Colpaert FC, Slangen JL (eds) Drug discrimination: applications in CNS pharmacology. Elsevier, Amsterdam, pp 211–218
Pomerleau OF, Pomerleau CS (1984) Neuroregulators and the reinforcement of smoking: towards a biobehavioral explanation. Neurosci Biobehav Rev 8:503–513
Romano C, Goldstein A, Jewell NP (1981) Characterization of the receptor mediating the nicotine discriminative stimulus. Psychopharmacology 74:310–315
Rose JE, Jarvik ME, Ananda S (1984a) Nicotine preference increases after cigarette deprivation. Pharmacol Biochem Behav 20:55–58
Rose JE, Jarvik ME, Rose KD (1984b) Transdermal administration of nicotine. Drug Alcohol Depend 13:209–213
Rose JE, Herskovic JE, Trilling Y, Jarvik M (1985) Transdermal nicotine reduces cigarette craving and nicotine preference. Clin Pharmacol Ther 38:450–456
Rosecrans JA (1979) Nicotine as a discriminative stimulus to behavior: its characterization and relevance to smoking behavior. NIDA Res Monogr 23:58–69
Schechter MD, Jellinek P (1975) Evidence for a cortical locus for the stimulus effect of nicotine. Eur J Pharmacol 34:65–73
Schechter MD, Rosecrans JA (1972a) Nicotine as a discriminative cue in rats: inability of related drugs to produce a nicotine-like cueing effect. Psychopharmacologia 27:379–387
Schechter MD, Rosecrans JA (1972b) Effect of mecamylamine on discrimination between nicotine- and arecoline-produced cues. Eur J Pharmacol 17:179–182
Schneider NG, Jarvik ME, Forsythe AB (1984) Nicotine vs placebo gum in the alleviation of withdrawal during smoking cessation. Addict Behav 9:149–156
Stolerman IP, Pratt JA, Garcha HS, Giardini V, Kumar R (1983) Nicotine cue in rats analysed with drugs acting on cholinergic and 5-hydroxytryptamine mechanisms. Neuropharmacology 22:1029–1037
Stolerman IP, Garcha HS, Pratt JA, Kumar R (1984) Role of training dose in discrimination of nicotine and related compounds by rats. Psychopharmacology 84:413–419
Taylor P (1985) Cholinergic agonists. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. MacMillan, New York, pp 105–107
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Craft, R.M., Howard, J.L. Cue properties of oral and transdermal nicotine in the rat. Psychopharmacology 96, 281–284 (1988). https://doi.org/10.1007/BF00216050
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00216050