Skip to main content
Log in

Dissociations between the locomotor stimulant and depressant effects of nicotinic agonists in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The effects of nicotine and related compounds on locomotor activity were compared in experimentally naive rats and in animals chronically exposed to nicotine and the photocell test chambers. In experimentally naive rats, all nicotinic compounds decreased locomotion in a dose-related manner and the rank order of potency was (−)-nicotine>(+)-nornicotine>(+)-nicotine > cytisine > lobeline > anabasine. Mecamylamine attenuated the locomotor depressant effects of most of the agonists, except lobeline. In rats previously exposed to nicotine and the test apparatus for several weeks, (−)-nicotine increased locomotor activity in a dose-related manner, with a maximal increase to 400% of baseline at a dose of 0.4 mg/kg. One or more doses of (+)-nicotine, (+)-nornicotine and anabasine also increased locomotor activity in these animals, although the maximal effects seen were in all cases less than the maximal effect of (−)-nicotine. Cytisine and lobeline failed to increase locomotor activity at any dose tested. These conclusions were not altered by consideration of the time-courses for the effects of the different drugs. Thus, the results confirm that the locomotor stimulant and depressant effects of nicotine can be dissociated from each other, a finding that may be explained by differences in their actions at nicotinic receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abood LG, Maiti A, Grassi S, Salles KS (1987) The biochemical and functional nature of the nicotine receptor in rat brain. In: Martin WR, Van Loon GR, Iwamoto ET, Davis L (eds) Tobacco smoking and nicotine: a neurobiological approach. Advances in Behavioral Biology, vol. 31. Plenum, New York, pp 401–411

    Google Scholar 

  • Benwell MEM, Balfour DJK (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856

    PubMed  Google Scholar 

  • Clarke PBS (1992) The fall and rise of neuronalα-bungarotoxin binding proteins. Trends Pharmacol Sci 13:407–413

    Article  PubMed  Google Scholar 

  • Clarke PBS, Kumar R (1983a) The effects of nicotine on locomotor activity in non-tolerant and tolerant rats. Br J Pharmacol 78:329–337

    Google Scholar 

  • Clarke PBS, Kumar R (1983b) Characterization of the locomotor stimulant action of nicotine in tolerant rats. Br J Pharmacol 80:587–594

    PubMed  Google Scholar 

  • Clarke PBS, Fu DS, Jakubovic A, Fibiger HC (1988) Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats. J Pharmacol Exp Ther 246:701–708

    PubMed  Google Scholar 

  • de la Garza R, McGuire TJ, Freedman R, Hoffer BJ (1987) Selective antagonism of nicotine actions in the rat cerebellum withα-bungarotoxin. Neuroscience 23:887–891

    Article  PubMed  Google Scholar 

  • Deneris ES, Connolly J, Rogers SW, Duvoisin R (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors. Trends Pharmacol Sci 12:34–40

    Article  PubMed  Google Scholar 

  • Garcha HS, Thomas P, Spivak CE, Wonnacott S, Stolerman IP (1993) Behavioural and ligand-binding studies in rats with 1-acetyl-4-methylpiperazine, a novel nicotinic agonist. Psychopharmacology 110:347–354

    PubMed  Google Scholar 

  • Goldberg SR, Risner ME, Stolerman IP, Reavill C, Garcha HS (1989) Nicotine and some related compounds: effects on schedule-controlled behaviour and discriminative properties in rats. Psychopharmacology 97:295–302

    Article  PubMed  Google Scholar 

  • Ksir CJ, Hakan RL, Hall DP, Kellar KJ (1985) Exposure to nicotine enhances the behavioral stimulant effect of nicotine and increases binding of [3H]acetylcholine to nicotinic receptors. Neuropharmacology 24:527–531

    Article  PubMed  Google Scholar 

  • Ksir CJ, Hakan RL, Kellar KJ (1987) Chronic nicotine and locomotor activity: influences of exposure dose and test dose. Psychopharmacology 92:25–29

    Article  PubMed  Google Scholar 

  • London ED, Connolly RJ, Szikszay M, Walmsley JK, Dam M (1988) Effects of nicotine on local cerebral glucose utilization in the rat. J Neurosci 8:3920–3928

    PubMed  Google Scholar 

  • Lukas RJ (1989) Nicotinic acetylcholine receptor diversity: agonist binding and functional potency. In: Nordberg A, Fuxe K, Holmstedt B, Sundwall A (eds) Nicotinic receptors in the CNS: their role in synaptic transmission. Prog. Brain Res vol 31. Elsevier, Amsterdam, pp 117–127

    Google Scholar 

  • Marks MJ, Romm E, Campbell SM, Collins AC (1989a) Variation of nicotinic binding sites among inbred strains. Pharmacol Biochem Behav 33:679–689

    Article  PubMed  Google Scholar 

  • Marks MJ, Stitzel JA, Collins AC (1989b) Genetic influences on nicotine responses. Pharmacol Biochem Behav 33:667–678

    Article  PubMed  Google Scholar 

  • Museo E, Wise RA (1990) Locomotion induced by ventral tegmental microinjections of a nicotinic agonist. Pharmacol Biochem Behav 35:735–737

    Google Scholar 

  • Nordberg A, Adem A, nilsson L, Romanelli L, Zhang X (1988) Heterogenous cholinergic nicotinic receptors in the CNS. In Clementi F et al. (eds) Nicotinic acetylcholine receptors in the nervous system. Springer, Berlin, pp 331–350

    Google Scholar 

  • Pert A, Chiueh CC (1986) Effects of intracerebral nicotinic agonists on locomotor activity: involvement of mesolimbic dopamine. Soc Neurosci Abstr 12:917

    Google Scholar 

  • Reavill C, Stolerman IP (1990) Locomotor activity in rats after administration of nicotinic agonists intracerebrally. Br J Pharmacol 99:273–278

    PubMed  Google Scholar 

  • Reavill C, Spivak CE, Stolerman IP, Waters JA (1987) Isoarecolone can inhibit nicotine binding and produce nicotine-like discriminative stimulus effects in rats. Neuropharmacology 26:789–792

    Article  PubMed  Google Scholar 

  • Reavill C, Jenner P, Kumar R, Stolerman IP (1988) High-affinity binding of [3H](−)-nicotine to rat brain membranes and its inhibition by analogues of nicotine. Neuropharmacology 27:235–241

    Article  PubMed  Google Scholar 

  • Reavill C, Walther B, Stolerman IP, Testa B (1990a) Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline. Neuropharmacology 29:619–624

    Article  PubMed  Google Scholar 

  • Reavill C, Waters JA, Stolerman IP, Garcha HS (1990b) Behavioural effects of the nicotinic agonists N-(3-pyridylmethyl) pyrrolidine and isoarecolone in rats. Psychopharmacology 102:521–528

    Article  PubMed  Google Scholar 

  • Risner ME, Goldberg SR, Prada JA, Cone EJ (1985) Effects of nicotine, cocaine and some of their metabolites on schedule-controlled responding by beagle dogs and squirrel monkeys. J Pharmacol Exp Ther 234:113–119

    PubMed  Google Scholar 

  • Romano C, Goldstein A, Jewell NP (1981) Characterization of the receptor mediating the nicotine discriminative stimulus. Psychopharmacology 74:310–315

    Article  PubMed  Google Scholar 

  • Stolerman IP (1990a) Behavioural pharmacology of nicotine in animals. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology: molecular, cellular, and behavioural aspects. Oxford Science Publications, Oxford, pp 278–306

    Google Scholar 

  • Stolerman IP (1990b) Behavioural pharmacology of nicotine: implications for multiple brain nicotinic receptors. In: Bock GR, Marsh J (eds) The biology of nicotine dependence. Ciba Foundation Symposium 152. Wiley, Chichester, pp 3–16

    Google Scholar 

  • Stolerman IP, Fink R, Jarvik ME (1973) Acute and chronic tolerance to nicotine measured by activity in rats. Psychopharmacologia 30:329–342

    Google Scholar 

  • Stolerman IP, Bunker P, Jarvik ME (1974) Nicotine tolerance in rats: role of dose and dose interval. Psychopharmacologia 34:317–324

    Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

  • Stolerman IP, Albuquerque EX, Garcha HS (1992) Behavioural effects of anatoxin, a potent nicotinic agonist, in rats. Neuropharmacology 31:311–314

    Article  PubMed  Google Scholar 

  • Williams M, Robinson JL (1984) Binding of the nicotinic cholinergic antagonist, dihydro-β-erythroidine, to rat brain tissue. J Neurosci 4:2906–2911

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stolerman, I.P., Garcha, H.S. & Mirza, N.R. Dissociations between the locomotor stimulant and depressant effects of nicotinic agonists in rats. Psychopharmacology 117, 430–437 (1995). https://doi.org/10.1007/BF02246215

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246215

Key words

Navigation