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Role of calcium channels in effects of antidepressant drugs on responsiveness to pain

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Abstract

The effect of acute and chronic treatment with three antidepressant drugs on the cortical L-type calcium channel (measured as [3H]nitrendipine binding sites) and on the responsiveness to pain (assessed in the hot-plate test) was tested on the Wistar rat. Acute administration of antidepressants did not affect the characteristics of calcium channels and did not significantly prolong the hot-plate latency. However, a combination of antidepressants with nifedipine brought about analgesia. Chronic administration of imipramine did not significantly affect the characteristics of calcium channels but produced a moderate analgesic effect. In contrast, chronic administration of citalopram and chlorprothixene increased the density of [3H]nitrendipine binding sites and induced hyperalgesia, which was nullified by acute administration of nifedipine. The results confirm that calcium channels may be involved in analgesia and hyperalgesia and indicate that chronic treatment with some antidepressant may induce an increase in the density of cortical calcium channels.

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References

  • Antkiewicz-Michaluk L (1985) Action of antidepressant neuroleptics chlorprothixene and levomepromazine of the central noradrenergic system comparison with other antidepressants. Pol J Pharmacol Pharm 37:667–677

    Google Scholar 

  • Antkiewicz-Michaluk L (1986) The influence of chronic treatment with antidepressant neuroleptics on the central serotonin system. Pol J Pharmacol Pharm 38:359–370

    PubMed  Google Scholar 

  • Antkiewicz-Michaluk L, Michaluk J, Romańska I, Vetulani J (1990a) Effect of repetitive electroconvulsive treatment on sensitivity to pain and on [3H]nitrendipine binding sites in cortical and hippocampal membranes. Psychopharmacology 101:240–243

    PubMed  Google Scholar 

  • Antkiewicz-Michaluk L, Michaluk J, Romańska I, Vetulani J (1990b) Cortical dihydropyridine binding sites and a behavioral syndrome in morphine-abstinent rats. Eur J Pharmacol 180:129–135

    Article  PubMed  Google Scholar 

  • Bellemann P, Ferrz D, Lübbecke F, Glossmann H (1981) [3H]Nitrendipine, a potent calcium antagonist binds with high affinity to cardiac membranes. Arzneimittelforschung 31:2064–2067

    PubMed  Google Scholar 

  • Benedek G, Szikszay M (1984) Potentiation of thermoregulatory and analgesic effects of morphine by calcium antagonists. Pharmacol Res Commun 16:1009–1018

    PubMed  Google Scholar 

  • Biegon A, Samuel D (1980) Interaction of tricyclic antidepressants with opiate receptors. Biochem Pharmacol 29:460–462

    Article  PubMed  Google Scholar 

  • Bray GA (1960) A simple efficient liquid scintillator for counting solutions in a liquid scintillation counter. Anal Biochem 1:279–285

    Article  Google Scholar 

  • Bunney WE, Davis JM (1967) Norepinephrine in depressive reaction. Arch Gen Psychiatry 13:483–494

    Google Scholar 

  • Chapman D, Way E (1982) Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator and a ionophore. Br J Pharmacol 75:389–396

    PubMed  Google Scholar 

  • Contreras E, Tamayo L, Amigo M (1988) Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance. Eur J Pharmacol 148:463–466

    Article  PubMed  Google Scholar 

  • Coppen A (1967) The biochemistry of affective disorders. Br J Psychiatry 113:1237–1264

    PubMed  Google Scholar 

  • Crowder J, Norris D, Bradford H (1986) Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes. Neuropharmacology 35:2501–2510

    Google Scholar 

  • Daniel W, Adamus A, Melzacka M, Szymura J, Vetulani J (1981) Cerebral pharmacokinetics of imipramine in rats after single and multiple doses. Naunyn-Schmiedeberg's Arch Pharmacol 317:209–213

    Article  Google Scholar 

  • De Lorenzo RJ (1981) The calmodulin hypothesis of neurotransmission. Cell Calcium 2:365–385

    Article  PubMed  Google Scholar 

  • De Lorenzo RJ (1982) Calmodulin modulation of calcium signal in synaptic transmission. In: Bradford HF (ed) Neurotransmitter interaction and compartmentation. Plenum Press, New York, pp 101–120

    Google Scholar 

  • Dunnett CW (1955) A multiple comparison procedure for comparing several treatments with a control. J Am Statist Assoc 50:1096–1121

    Google Scholar 

  • Ferreira SH (1980) Local analgesic effect of morphine on hyperalgesia induced by cAMP, Ca++, isoprenaline and PGE2. Adv Prostaglandin Thromboxane Res 8:1207–1215

    PubMed  Google Scholar 

  • Fink M (1979) Efficacy of ECT. Lancet i:1303–1304

    Article  Google Scholar 

  • Guerrero-Munoz F, Cerreta K, Guerrero M, Way E (1979) Effect of morphine on synaptosomal Ca++ uptake. J Pharmacol Exp Ther 209:132–136

    PubMed  Google Scholar 

  • Harris RA, Yamamoto H, Loh H, Way L (1977) Discrete changes in brain calcium with morphine analgesia, tolerance-dependence and abstinence. Life Sci 20:501–506

    Article  PubMed  Google Scholar 

  • Heschler J, Rosenthal W, Trautwein W, Schultz G (1987) The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 325:445–447

    Article  PubMed  Google Scholar 

  • Hoffmeister F, Tettenborn D (1986) Calcium agonists and antagonists of dihydropyridine type: antinociceptive effects, interference with opiate-μ-receptor agonists and neuropharmacological action in rodents. Psychopharmacology 90:299–307

    PubMed  Google Scholar 

  • Hyttel J (1982) Citalopram — Pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Progr Neuropsychopharmacol Biol Psychiatry 6:277–295

    Article  Google Scholar 

  • Jorgensen A (1986) Metabolism and pharmacokinetics of antipsychotic drugs. Prog Drug Metab 9:111–174

    Google Scholar 

  • Kamikubo K, Niwa M, Fugimura H, Miura K (1983) Morphine inhibits depolarization-dependent calcium uptake by synaptosomes. Eur J Pharmacol 95:149–150

    Article  PubMed  Google Scholar 

  • Lee R, Spencer PSJ (1977) Antidepressants and pain: a review of pharmacological data supporting the use of certain tricyclics in chronic pain. J Int Med Res 5 [Suppl 1]:145–156

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  Google Scholar 

  • Maj J, Przegalinski E, Mogilnicka E (1984) Hypotheses concerning the mechanism of action of antidepressant drugs. Rev Physiol Biochem Pharmacol 100:1–74

    PubMed  Google Scholar 

  • Middlemiss D (1985) The calcium channel activator, Bay K8644, enhances K+ evoked efflux of acetylcholine and noradrenaline from brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 331:114–116

    Article  Google Scholar 

  • Middlemiss D, Spedding M (1985) A functional correlate for the dihydropyridine binding site in rat brain. Nature 314:94–96

    Google Scholar 

  • Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52

    PubMed  Google Scholar 

  • Mogilnicka E, Czyrak A, Maj J (1987) Dihydropyridine calcium channel antagonists reduce immobility in the mouse behavioral despair test; antidepressants facilitate nifedipine action. Eur J Pharmacol 138:413–416

    Article  PubMed  Google Scholar 

  • Panza G, Grebb JA, Sanna E, Wright AG, Hanbauer I (1985) Evidence for down-regulation of 3H-nitrendipine recognition sites in mouse brain after long-term treatment with nifedipine or verapamil. Neuropharmacology 24:1113–1117

    Article  PubMed  Google Scholar 

  • Ravn J, Scharff A, Aaskoven O (1980) 20 Jahre Erfahrungen mit Chlorprothixen. Pharmakopsychiatrie 13:34–40

    Google Scholar 

  • Ross DH, Cardenos HL (1979) Nerve cell calcium as a messenger for opiate and endorphin actions. Adv Biochem Psychopharmacol 20:301–336

    PubMed  Google Scholar 

  • Sulser F, Vetulani J, Mobley PL (1978) Mode of action of antidepressant drugs. Biochem Pharmacol 27:257–261

    Article  PubMed  Google Scholar 

  • Triggle D, Janis R (1984) The 1,4-dihydropyridine receptor: a regulatory component of the CA++ channel. J Cardiovasc Pharmacol 6:949–955

    PubMed  Google Scholar 

  • Von Bormann B, Boldt J, Sturm G, Kling D, Weidler B, Lohmann E, Hempelmann G (1985) Calciumantagonisten in der Analgesie. Additive Analgesie durch Nimodipin während cardiochirurgischer Eingriffe. Anaesthetist 34:429–435

    Google Scholar 

  • Whittaker VP, Barker LA (1972) The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles. In: Fried R (ed) Methods of neurochemistry, vol. 2. Dekker, New York, pp 1–52

    Google Scholar 

  • Yaksh TL (1978a) Opiate receptors for behavioral analgesia resemble those related to the depression of spinal nociceptive neurons. Science 199:1231–1233

    PubMed  Google Scholar 

  • Yaksh TL (1978b) Narcotic analgetics: CNS sites and mechanisms as revealed by intracerebral injection techniques. Pain 4:299–359

    Article  PubMed  Google Scholar 

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Antkiewicz-Michaluk, L., Romańska, I., Michaluk, J. et al. Role of calcium channels in effects of antidepressant drugs on responsiveness to pain. Psychopharmacology 105, 269–274 (1991). https://doi.org/10.1007/BF02244321

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  • DOI: https://doi.org/10.1007/BF02244321

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