Abstract
The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive treatment (ECS). In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, inhibited the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent and ECS-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg IP that does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg IP, significantly reduced hypermotility produced by apomorphine in morphine abstinent or ECS-treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy.
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Antkiewicz-Michaluk L, Michaluk J, Romańska I, Vetulani J (1990a) Cortical dihydropyridine binding sites and a behavioral syndrome in morphine-abstinent rats. Eur J Pharmacol 180:129–135
Antkiewicz-Michaluk L, Michaluk J, Romańska I, Vetulani J (1990b) Effect of repetitive electroconvulsive treatment on sensitivity to pain and on [3H]nitrendipine binding sites in the cortical and hippocampal membranes. Psychopharmacology 101:240–243
Antkiewicz-Michaluk L, Michaluk J, Romanska I, Vetulani J (1991) Role of calcium channels in effects of antidepressant drugs on responsiveness to pain. Psychopharmacology 105:269–274
Antkewicz-Michaluk L, Michaluk J, Romanska I, Vetulani J (1993) Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine. Psychopharmacology, (in press)
Argiolas A, Melis MR, Gessa GL (1989) Calcium channel inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats. Eur J Pharmacol 166:515–518
Argiolas A, Melis MR, Stancampiano R, Gessa GL (1990) ω-Conotoxin prevents apomorphine- and oxytocin-induced penile erection and yawning in male rats. Pharmacol Biochem Behav 37:253–257
Bednarczyk B, Vetulani J (1977) Stimulatory and inhibitory action of clonidine on the locomotor activity in the rat. Pol J Pharmacol Pharm 29:219–229
Bergstrom DA, Kellar KJ (1979) Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature 287:464–466
Bhargava HN, Gulati A (1990) Modification of brain and spinal cord dopamine D1 receptors labeled with [3H]SCH 23390 after morphine withdrawal from tolerant and physically dependent rats. J Pharmacol Exp Ther 252:901–907
Bischoff S, Bittiger H, Delini-Stula A, Ortman R (1982) Septohippocampal system: target for substituted benzamides. Eur J Pharmacol 79:225–232
Bolger GT, Lesieur P, Basile A, Skolnick P (1988) Modulation of neurotransmitter metabolism by dihydropyridine calcium channel ligands in mouse brain. Brain Res 438:101–107
Bongianni F, Carla V, Moroni F, Pellegrini-Giampietro DE (1986) Calcium channel inhibitors suppress the morphine-withdrawal syndrome in rats. Br J Pharmacol 88:561–567
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 (1989a) Central and peripheral effects of the dihydropyridine calcium channel activator BAY K 8644. Eur J Pharmacol 160:339–347
Bourson A, Gower AJ, Mir AK, Moser PC (1989b) The effects of dihydropyridine compounds in behavioral tests of dopaminergic activity. Br J Pharmacol 98:1312–1318
Carter CJ, L'Heureux R, Scatton B (1988) Differential control by N-methyl-D-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study. J Neurochem 51:462–468
Clow DW, Jhamandas K (1989) Characterization of L-glutamate action on the release of endogenous dopamine from the rat caudate-putamen. J Pharmacol Exp Ther 248:722–728
Costall B, Marsden CD, Naylor RJ, Pycock CJ (1977a) Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei. Brain Res 123:89–111
Costall B, Naylor RJ, Cannon JG, Lee T (1977b) Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens. J Pharm Pharmacol 29:337–342
Czyrak A, Mogilnicka E, Maj J (1989) Dihydropyridine calcium channel antagonists as antidepressant drugs in mice and rats. Neuropharmacology 28:229–233
Deakin JFW, Owen F, Cross AJ, Dashwood MJ (1981) Studies on possible mechanisms of action of electroconvulsive therapy: effects of repeated electrically-induced seizures on rat brain receptors for monoamines and other neurotransmitters. Psychopharmacology 73:345–349
Grebb JA, Shelton RC, Freed WJ (1987) Diltiazem or verapamil prevents haloperidol-induced apomorphine supersensitivity in mice. J Neural Transm 68:241–255
Green AR, Heal DJ, Grahame-Smith DG (1977) Further observations on the effect of repeated electroconvulsive shock on the behavioral responses of rats produced by increases in the functional activity of brain 5-hydroxytryptamine and dopamine. Psychopharmacology 52:195–200
Green AR, Heal DJ, Johnson P, Laurence BE, Nimgaonkar VL (1983) Antidepressant treatments: effects in rodents on dose-response curves on 5-hydroxytryptamine and dopamine-mediated behaviours and 5HT2-receptor function in frontal cortex. Br J Pharmacol 80:377–385
Gulati A, Srimal RC, Dhawan KN, Dhawan BN (1987) On the mechanism of potentiation of apomorphine-induced stereotypy due to electroconvulsive shock. Neuropharmacology 26:1233–1237
Heal DJ, Green AR (1978) Repeated electroconvulsive shock increases the behavioral responses of rats to injections of both dopamine and dibutyryl cyclic AMP into the nucleus accumbens. Neuropharmacology 17:1085–1087
Iversen SD, Joyce EM (1978) Effect in the rat of chronic morphine treatment on the behavioral response to apomorphine. Br J Pharmacol 62 P 390P-391P
Jackson EA, Kelly PH (1984) Effects of intranigral injections of dopamine agonists and antagonists, glycine, muscimol and N-methyl-D,L-aspartate on locomotor activity. Brain Res Bull 13:309–317
Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522
Klimek V, Nielsen M (1987) Chronic treatment with antidepressants decreases the number of3H-SCH 23390 binding sites in rat striatum and limbic system. Eur J Pharmacol 139:163–169
Köhler C, Haglund L, Ogren S-O, Angeby T (1981) Regional blockade by neuroleptic drugs on in vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies. J Neural Transm 52:163–173
Maj J, Grabowska M, Gajda L (1972) Effect of apomorphine on motility in rats. Eur J Pharmacol 17:208–214
Melzacka M, Wiszniowska G, Vetulani J (1978) The distribution of apomorphine in rat brain: possible behavioral correlates. Pol J Pharmacol Pharm 30:309–317
Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52
Modigh K, Balldin J, Eriksson E, Granérus AK, Wålinder J (1984) Increased responsiveness of dopamine receptors after ECT — a review of experimental and clinical evidence. In: Lerer B, Weiner RR, Belmaker RH (eds) ECT: basic mechanisms. Libbey, London Paris, pp 18–27
Pijnenburg AJJ, Honig WMM, Van Rossum JM (1975) Antagonism of apomorphine- and amphetamine-induced stereotyped behaviour by injection of low doses of haloperidol into the caudate nucleus and the nucleus accumbens. Psychopharmacologia 45:65–71
Pijnenburg AJJ, Honig WMM, Van der Heyden JAM, Van Rossum JM (1976) Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol 35:45–58
Pucilowski O, Kostowski W (1988) Diltiazem suppresses apomorphine-induced fighting and pro-aggressive effect of withdrawal from chronic ethanol or haloperidol in rats. Neurosci Lett 93:96–100
Ramkumar V, El-Fakahany E (1988) Prolonged morphine treatment increases rat brain dihydropyridine binding sites: possible involvement in development of morphine dependence. Eur J Pharmacol 146:73–83
Ross DH, Cardenos HL (1979) Nerve cell calcium as a messenger for opiate and endorphin actions. Adv Biochem Psychopharmacol 20:301–336
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32:229–313
Sharp T, Kingston J, Grahame-Smith DG (1990) Repeated ECS enhances dopamine D-1 but not D-2 agonist-induced behavioral responses in rats. Psychopharmacology 100:110–114
Staton DM, Solomon PR (1984) Microinjections ofd-amphetamine into the nucleus accumbens and caudate-putamen differentially affect stereotypy and locomotion in rats. Physiol Psychol 12:159–162
Tabernero C, Pardo B, Garcia de Yebenes J (1991) Efecto de los bloqueantes de canales de calcio sobre la rotacion inducida por apomorfina y anfetamina en ratas lesionadas con 6-OH-DA. Arch Neurobiol (Madr) 54:49–53
Vetulani J, Antkiewicz-Michaluk L, Sansone M (1992) Antagonistic and facilitatory interactions of nifedipine with psychotropic drugs. Behav Pharmacol 3 [suppl. 1]:92
Wedzony K, Gołembiowska K, Maj J (1991) A search for the effects of NMDA on the release of dopamine from the nucleus caudatus. Monit Mol Neurosci 1:321–324
Wiszniowksa-Szafraniec G, Danek L, Reichenberg K, Vetulani J (1983) Facilitation by α-adrenolytics of apomorphine gnawing behavior: depression of threshold apomorphine concentration in the striatum of the rat. Pharmacol Biochem Behav 19:19–21
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Antkiewicz-Michaluk, L., Michaluk, J., Romańska, I. et al. Differential involvement of voltage-dependent calcium channels in apomorphine-induced hypermotility and stereotypy. Psychopharmacology 113, 555–560 (1994). https://doi.org/10.1007/BF02245239
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DOI: https://doi.org/10.1007/BF02245239