Summary
It has previously been demonstrated that the muscarinic antagonist scopolamine induces hyperactivity in rodents, which is reversed by physostigmine but not by directly acting agonists such as pilocarpine. This may suggest that non-muscarinic actions of physostigmine may be responsible for its reversal of scopolamine-induced hyperactivity. We have found, in male Wistar rats, whose activity was measured on electromagnetic detector plates, that the central nicotinic receptor antagonist mecamylamine (3 mg/kg) reverses the blockade of scopolamine-induced behavioural activation induced by physostigmine. This suggests that activation of nicotinic receptors can counteract the effects of muscarinic blockade. Interestingly, however, treatment with nicotine does not block scopolamine-induced hyperactivity, suggesting that the exogenous and endogenous ligands may have different receptor or neuronal substrates.
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References
Bauer RH (1982) Age-dependent effects of scopolamine on avoidance, locomotor activity and rearing. Behav Brain Res 5: 261–279
Bushnell PJ (1987) Effects of scopolamine on locomotor activity and metabolic rate in mice. Physiol Biochem Behav 26: 195–198
Clarke PBS, Kumar R (1983) The effects of nicotine on locomotor activity in non-tolerant and tolerant rats. Br J Pharmacol 78: 329–337
DeBelleroche J, Bradford HF (1978) Biochemical evidence for the presence of presynaptic receptors on dopaminergic terminals. Brain Res 142: 53–68
Desole MS, Miele M, Enrico P, Esposito G, Fresu L, DeNatale G, Miele E (1992) Effects of cortical ablation on apomorphine- and scopolamine-induced changes in dopamine turnover and ascorbic acid catabolism in the rat striatum. Eur J Pharmacol 219: 67–74
Giorguieff-Chesselet MF, Kemel ML, Wandscheer D, Glowinski J (1979) Regulation of dopamine release by presynaptic nicotine receptors in rat striatal slices: effect of nicotine at low concentrations. Life Sci 25: 1257–1262
Grenhoff J, Aston-Jones G, Svensson TH (1986) Nicotinic effects on the firing pattern of midbrain dopamine neurons. Acta Physiol Scand 21: 351–358
Grenhoff J, Svensson TH (1992) Nicotinic and muscarinic components of rat brain dopamine synthesis stimulation induced by physostigmine. Naunyn Schmiedebergs Arch Pharmacol 346: 395–398
Haikala H, Ahtee L (1988) Antagonism of the nicotine-induced changes of the striatal dopamine metabolism in mice by mecamylamine and pempidine. Naunyn Schmiedebergs Arch Pharmacol 338: 169–173
Messamore E, Ogane N, Giacobini E (1993) Cholinesterase inhibitor effects on extracellular acetylcholine in rat striatum. Neuropharmacology 32: 291–296
Nilsson L, Adem A, Hardy J, Winblad B, Nordberg A (1987) Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors? J Neural Transm 70: 357–368
O'Neill MF, Dourish CT, Iversen SD (1991) Evidence for an involvement of Dl and D2 dopamine receptors mediating nicotine-induced hyperactivity in rats. Psychopharmacology 104: 343–350
Ray CA, Blin J, Chase TN, Piercey MF (1992) Effects of cholinergic agonists on regional brain energy metabolism in the scopolamine-treated rat. Neuropharmacology 31: 1193–1199
Reavill C, Stolerman IP (1990) Locomotor activity in rats after administration of nicotinic agonists intracerebrally. Br J Pharmacol 99: 273–278
Robbins TW (1977) A critique of methods available for the measurement of spontaneous motor activity. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 7. Plenum Press, New York, pp 37–82
Rosecrans JA, Meltzer LT (1981) Central sites and mechanisms of action of nicotine. Neurosci Biobehav Rev 5: 497–501
Sanberg PR, Henault MA, Hagenmeyer-Houser SH, Russell KH (1987) The topography of amphetamine and scopolamine-induced hyperactivity: toward an activity print. Behav Neurosci 101: 131–133
Sansone M, D'Udine B, Renzi P, Vetulani J (1987) Antihistaminics enhance morphine-, but not amphetamine- and scopolamine-induced hyperactivity in mice. Psychopharmacology 93: 155–157
Shannon HE, Peters SC (1990) A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice. J Pharmacol Exp Ther 255: 549–553
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O'Neill, M.F., Fernández, A.G., Gristwood, R.W. et al. Mecamylamine reverses physostigmine-induced attenuation of scopolamine-induced hyperactivity. J. Neural Transmission 96, 9–18 (1994). https://doi.org/10.1007/BF01277924
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DOI: https://doi.org/10.1007/BF01277924