Summary
In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/ kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blaustein MP, Nachshen DA, Drapeau P (1981) Excitation-secretion coupling: The role of calcium. In: Stjärne L, Hedqvist P, Lagercrantz H, Wennmalm Å (eds) Chemical neurotransmission. Academic Press, London, pp 125–138
Bolger GT, Wiessman BA, Skolnick P (1985) The behavioral effects of the calcium agonist BAY K 8644 in the mouse: antagonism by the calcium antagonist nifedipine. Naunyn Schmiedebergs Arch Pharmacol 328: 370–377
Carlén PL, Gurevich N, Durand D (1982) Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons. Science 215: 306–309
Engel J (1977) Neurochemical aspects of the euphoria induced by dependence-producing drugs. In: Ideström C-M (ed) Recent advances in the study of alcoholism. Excerpta Medica, Amsterdam (International congress series no 407, pp 16–22)
Engel J (1985) Influence of age and hormones on the stimulatory and sedative effects of ethanol. In: Rydberg U, Alling C, Engel J (eds) Alcohol and the developing brain. Raven Press, New York, pp 57–67
Engel JA, Johannessen K, Liljequist S, Goldstein M (1986) Activation of α2-adrenoreceptors enhances haloperidol-induced suppression of operant behavior. J Neural Transm 66: 107–120
Engel J, Liljequist S (1983) The involvement of different central neurotransmitters in mediating stimulatory and sedative effects of ethanol. In: Pohorecky L, Brick J (eds) Stress and alcohol use. Elsevier, New York, pp 153–169
Friedman M, Erickson CK, Leslie SW (1980) Effects of acute and chronic ethanol administration on whole mouse brain synaptosomal calcium influx. Biochem Pharmacol 29: 1903–1908
Gonon FG, Fombariet CM, Buda MJ, Pujol FJ (1981) Electrochemical treatment of pyrolytic carbon fiber electrodes. Anal Chem 53: 1386–1389
Greenberg DA, Cooper EC (1984) Effect of ethanol on3H-nitrendipine binding to calcium channels in brain membranes. Alcoholism (NY) 8: 568–571
Harris RA, Hood WF (1980) Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther 213: 562–568
Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioural effects of nimodipine in animals. Arzneimittelforschung 32: 347–360
Holman RB, Snape BM (1985) Effects of ethanol in vitro and in vivo on the release of endogenous catecholamines from specific regions of rat brain. J Neurochem 44: 357–363
Imperato A, Di Chiara G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239: 219–228
Leslie SW, Barr E, Chandler J, Farrar RP (1983) Inhibition of fast and slow-phase depolarisation-dependent calcium uptake by ethanol. J Pharmacol Exp Ther 225: 571–575
Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235: 46–52
Murphy JM, Cunningham SD, McBride WI (1985) Effects of 250 mg% ethanol on monoamine and amino acid release from rat striatal slices. Brain Res Bull 14: 439–442
Naranjo CA, Sullivan J, Lawrin MO, Sellers EM (1987) Strategies for the identification and testing of new pharmacological modulators of ethanol consumption. In: Engel J, Oreland L (eds) Brain reward systems and abuse. Raven Press, New York, pp 129–145
Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channels with different calcium channel sensitivity. Nature 316: 440–443
O'Neill RD, Fillenz M, Sundstrom L, Rawlins JNP (1984) Voltammetrically monitored brain ascorbate as an index of excitatory amino acid release in the unrestrained rat. Neurosci Lett 52: 227–233
Osteryoung JG, Osteryoung RA (1985) Square wave voltammetry. Anal Chem 57: 101–110
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney
Pileblad E, Carlsson A (1986) In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain. J Neural Transm 66: 171–187
Pileblad E, Carlsson A (1987) The Ca2+-antagonist nimodipine decreases and the Ca2+-agonist Bay K 8644 increases catecholamine synthesis in mouse brain. Neuropharmacol 26: 101–105
Ramkumar V, El-Fakahany EE (1986) The current status of the dihydropyridine calcium channel antagonist binding sites in the brain. TIPS 6: 171–172
Rampe D, Janis RA, Triggle DJ (1984) Bay K 8644, a 1,4-dihydropyridine Ca+ + channel activator: dissociation of binding and functional effects in synaptosomes. J Neurochem 34: 1688–1692
Snape BM, Engel JA (1988) Ethanol enhances the calcium-dependent stimulus-induced release of endogenous dopamine from slices of rat striatum and nucleus accumbensin vitro. Neuropharmacology, in press
Svensson K (1986) Dopamine autoreceptor antagonists: a new class of central stimulants. Thesis. ISBN 91-7900-078-9
Wu PH, Fan T, Naranjo CA (1987) Increase in the brain regional depolarization-dependent Ca2+ uptake in rats preferring ethanol. Pharmacol Biochem Behav 27: 355–357
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Engel, J.A., Fahlke, C., Hulthe, P. et al. Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists. J. Neural Transmission 74, 181–193 (1988). https://doi.org/10.1007/BF01244784
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244784