Discriminative Stimulus Effects of Cholinergic Agonists and the Actions of Their Antagonists
Both muscarinic- and nicotinic-cholinergic agonists have been used for discrimination training, but only nicotine has been studied extensively. The limited information available suggests that the discriminative stimulus effects of drugs classified as muscarinic-cholinergic agonists are blocked competitively by atropine but not by ganglion-bloekers. The discriminative effects of nicotine are blocked non-competitively by ganglion-blocking drugs that penetrate into the CNS (e.g. mecamylamine), but they are not blocked by atropine. The specificity of the block is shown by the failure of mecamylamine to block several non-nicotinic drugs. The ganglion-blocking drug chlorisondamine penetrates poorly into the CNS when injected systemically; when injected in- traventricularly, it is a potent and specific nicotine antagonist with a 4-week duration of effect. Haloperidol attenuates discriminative effects of nicotine but this is not a specific block; there are marked reductions in response rate, the morphine stimulus is also attenuated, and other neuroleptics have much weaker effects. The results support the view that the discriminative effect of nicotine involves predominantly cholinoceptive sites, and they suggest that it is not mediated primarily by the dopamine system. The transduction mechanisms for the nicotine stimulus may include the receptor sites that mediate many of its other CNS effects, but more information is needed about possible subtypes of nicotinic receptors before definitive conclusions are possible.
KeywordsDopamine Midazolam Amphetamine Atropine Clonidine
Unable to display preview. Download preview PDF.
- Browne RG (1982) Discriminative stimulus properties of phencyclidine. In: Colpaert FC, Slangen JL (eds) Drug discrimination: applications in CNS pharmacology. Elsevier, Amsterdam, pp 109–122Google Scholar
- Garcha HS, Kumar R, Norris EA, Reavill C, Stolerman IP (1985) Long-term blockade of nicotine cue by chlorisondamine in rats. Br J Pharmacol 85:245PGoogle Scholar
- Giorguieff-Chesselet MF, Chéramy A, Glowinski J (1980) In vivo and in vitro studies on the presynaptic control of dopamine release from nerve terminals of the nigrostriatal dopaminergic neuron. In: Littauer UZ, Dudai Y, Silman I, Teichberg VI, Vogel Z (eds) Neurotransmitters and their receptors. Wiley, New York, pp 33–47Google Scholar
- Jung M, Costa L, Shearman GT, Kelly PH (1986) Discriminative properties of muscarinic agonists. Psychopharmacology 89:S46Google Scholar
- Overton DA (1969) Control of T-maze choice by nicotinic, antinicotinic, and antimuscarinic drugs. Proceeding of the 77th annual convention of American Psychological Association, p 869Google Scholar
- 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 155–185Google Scholar
- Rosecrans J A, 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, Amsterdam, pp 69–81Google Scholar
- Stolerman IP (1987) Psychopharmacology of nicotine: stimulus effects and receptor mechanisms. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 19. Plenum, New York, pp 421–465Google Scholar