Abstract
The dihydropyridine calcium channel antagonist nifedipine, tested in mice of CD-1, C57BL/6 and DBA/2 strains, at doses of 2.5, 5 and 10 mg/kg IP, had no significant effect on shuttle-box avoidance acquisition. Nifedipine also failed to affect performance retention in CD-1 mice subjected to a one-trial passive avoidance task (step-through). While ineffective alone, nifedipine strongly enhanced the shuttle-box avoidance facilitating action of amphetamine (1 and 2 mg/kg IP) in low performing CD-1 mice. The results indicate that although calcium channel blockers do not affect learning in avoidance paradigms in normal animals, they can interfere with the effects of other centrally acting drugs. Calcium antagonists might interfere with neuronal changes induced by amphetamine, but at present it is difficult to explain the strong avoidance facilitation produced by combinations of nifedipine and amphetamine. A possibility that the action of nifedipine on cerebral circulation is involved in the amphetamine-nifedipine interaction cannot be excluded.
Similar content being viewed by others
References
Antkiewicz-Michaluk L, Romanska I, Michaluk J, Vetulani J (1991) Role of calcium channels in effects of antidepressant drugs on responsiveness to pain. Psychopharmacology 105:269–274
Bammer G (1982) Pharmacological investigations of neurotransmitter involvement in passive avoidance responding: a review and some new results. Neurosci Biobehav Rev 6:247–296
Beck T, Kriegelstein J (1987) Local cerebral glucose utilization and local cerebral blood flow in conscious rats after administration of flunarizine. Naunyn-Schmiedebergs Arch Pharmacol 335:680–685
Bolger GT, Weissman BA, Skolnick P (1985) The behavioral effects of the calcium agonist BAY K 8644 in the mouse: antagonism by the calcium antagonist nifedipine. Naunyn-Schmiedeberg's Arch Pharmacol 328:373–377
Bolger GT, Rafferty MF, Crawley JN, Paul SM, Skolnick P (1986) Effects of calcium antagonists on phencyclidine behaviors. Pharmacol Biochem Behav 25:45–49
Bolger GT, Lesieur P, Basile AS, Skolnick P (1988) Modulation of neurotransmitter metabolism by dihydropyridine calcium channel ligands in mouse brain. Brain Res 438:101–107
Bone GHA, Majchrowicz E, Martin PR, Linnoila M, Nutt DJ (1989) A comparison of calcium antagonists and diazepam in reducing ethanol withdrawal tremors. Psychopharmacology 99:386–388
Bourson A, Moser PC (1990) Yawning induced by apomorphine, physostigmine or pilocarpine is potentiated by dihydropyridine calcium channel blockers. Psychopharmacology 100:168–172
Bourson A, Gower AJ, Mir AK, Moser PC (1989) The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity. Br J Pharmacol 98:1312–1318
Bovet D, Bovet-Nitti F, Oliverio A (1969) Genetic aspects of learning and memory in mice. Science 163:139–149
Cadet JL, Taylor E, Freed WJ (1988) The iminodipropionitrile (IDPN)-induced dyskinetic syndrome in mice: antagonism by calcium channel antagonist nifedipine. Pharmacol Biochem Behav 29:381–385
Czyrak A, Mogilnicka E, Siwanowicz J, Maj J (1990) Some behavioral effects of repeated administration of calcium channel antagonists. Pharmacol Biochem Behav 35:557–560
Dolin SJ, Little HJ (1986) Augmentation by calcium channel antagonists of general anaesthetic potency in mice. Br J Pharmacol 88:909–914
Essman WB (1971) Drug effects on learning and memory processes. Adv Pharmacol 9:241–330
Finger S, Green L, Tarnoff ME, Mortman KD, Andersen A (1990) Nimodipine enhances new learning after hippocampal damage. Exp Neurol 109:279–285
Gaggi R, Gianni AM (1990) Effects of calcium antagonists on biogenic amines in discrete brain areas. Eur J Pharmacol 181:187–197
Grebb JA (1986) Nifedipine and flunarizine block amphetamine-induced behavioral stimulation in mice. Life Sci 38:2375–2381
Gorelick DA, Bozewicz TR, Bridger WH (1975) The role of catecholamines in animal learning and memory. In: Friedhoff AJ (ed) Catecholamines and behavior, Vol 2, Neuropsychopharmacology. Plenum Press, New York, pp 1–30
Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioral effects of nimodipine in animals. Arzneimittelforschung Drug Res 32:347–360
Izquierdo I (1990) Nimodipine and the recovery of memory. TIPS 11:309–310
Levy A, Kong RM, Stillman MJ, Shukitt-Hale B, Kadar T, Rauch TM, Lieberman HR (1991) Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats. Pharmacol Biochem Behav 39:781–786
Martin MI, Lizasoain I, Leza JC (1990) Calcium channel blockers: effect on morphine-induced hypermotility. Psychopharmacology 101:267–270
Moron MA, Stevens CW, Yaksh TL (1990) The antiseizure activity of dihydropyridine calcium channel antagonists in the conscious rat. J Pharmacol Exp Ther 252:1150–1155
Nencini P, Woolverton WL (1988) Effects of nimodipine on the discriminative stimulus properties ofd-amphetamine in rats. Psychopharmacology 96: 40–44
Nordstrom O, Braesch-Andersen S, Bartfai T (1986) Dopamine release is enhanced while acetylcholine release is inhibited by nimodipine (Bay e 9736). Acta Physiol Scand 126:115–119
Oei TPS, King MG (1980) Catecholamines and aversive learning: a review. Neurosci Biobehav Rev 4:161–173
O'Neill SK, Bolger GT (1989) Anticonvulsant activity of MK-801 and nimodipine alone and in combination against pentylenetetrazole and strychnine. Pharmacol Biochem Behav 32:595–600
Pani L, Kuzmin A, Diana M, De Montis G, Gessa GL, Rossetti ZL (1990) Calcium receptor antagonists modify cocaine effects in the central nervous system differently. Eur J Pharmacol 190:217–221
Pileblad E, Carlsson A (1987) The Ca-antagonist nimodipine decreases and the Ca-agonist BAY K 8644 increases catecholamine synthesis in mouse brain. Neuropharmacology 26:101–105
Sandin M, Jasmin, S, Levere TE (1990) Aging and cognition: facilitation of recent memory in aged nonhuman primates by nimodipine. Neurobiol Aging 11:573–575
Sansone M, Vetulani J (1980) Facilitation of avoidance behavior by chlordiazepoxide and chlordiazepoxide-amphetamine combination: effect on performance. Pol J Pharmacol Pharm 32:125–131
Sansone M, Pavone F, Battaglia M, Daniel W, Vetulani J (1992) similar effects of nifedipine and hydralazine on both anaesthesia and hypermotility induced by pentobarbitone in mice. J Pharm Pharmacol 44:453–455
Sorkin EM, Clissold SP, Brogden RM (1985) Nifedipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs 30:182–274
Turkkan JS (1988) Behavioral performance effects of antihypertensive drugs: Human and animal studies. Neurosci Biobehav Rev 12:111–122
Weiner N (1985) Norepinephrine, epinephrine, and the sympathomimetic amines. In: Goodman Gilman A, Goodman LS, Rall TW, Murad F (eds) Goodman's and Gilman's the pharmacological basis of therapeutics. Macmillan, New York, pp 145–180
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vetulani, J., Battaglia, M., Castellano, C. et al. Facilitation of shuttle-box avoidance behaviour in mice treated with nifedipine in combination with amphetamine. Psychopharmacology 113, 217–221 (1993). https://doi.org/10.1007/BF02245700
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245700