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Differential effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine

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Abstract

The effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in miceacutely dependent on morphine were evaluated. Verapamil (10–80 mg/kg), diltiazem (20–120 mg/kg) and nicardipine (20–160 mg/kg), when administered subcutaneously, produced a dose-dependent reduction in forepaw tremor and weight loss during the abstinence reaction; jumping was also reduced by all three drugs, although the effect was not statistically significant in the case of nicardipine. By contrast, the calcium agonist Bay K 8644 (0.5–2 mg/kg, SC) increased forepaw tremor and weight loss, although this latter effect did not reach statistical significance. The effects of the calcium channel active drugs on the rotarod test were also explored, no correlation appearing with the results observed in abstinence (except for the jumping response), which suggests that the withdrawal results are not influenced by motor incoordination or unspecific CNS depression. These findings suggest that L-type calcium channels probably play an important role in withdrawal after acute morphine dependence. Taken together with other observations in chronic models, these results show that calcium channels are similarly involved in morphine abstinence after acute and chronic dependence, in contrast to the differences in the content and uptake of neuronal calcium induced by morphine under both conditions.

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References

  • Ahlijanian MK, Takemori AE (1985) Effects of (−)-N6-(R-phenyl-isopropyl)-adenosine (PIA) and caffeine on nociception and morphine-induced analgesia, tolerance and dependence in mice. Eur J Pharmacol 112:171–179

    Google Scholar 

  • Badaway AA-B, Evans CM, Evans M (1982) Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water. Br J Pharmacol 75:485–491

    Google Scholar 

  • Baeyens JM, Esposito E, Ossowska G, Samanin R (1987) Effects of peripheral and central administration of calcium channel blockers in the naloxone-precipitated abstinence syndrome in morphine-dependent rats. Eur J Pharmacol 137:9–13

    Google Scholar 

  • Barrios M, Baeyens JM (1988) Differential effects of calcium channel blockers and stimulants on morphine withdrawal in vitro. Eur J Pharmacol 152:175–178

    Google Scholar 

  • Bhargava HN (1978) The effects of divalent ions on morphine analgesia and abstinence syndrome in morphine-tolerant and dependent mice. Psychopharmacology 57:223–225

    Google Scholar 

  • Bickel WK, Stitzer ML, Liebson IA, Bigelow GE (1987) Acute physical dependence in man: effects of naloxone after brief morphine exposure. J Pharmacol Exp Ther 244:126–132

    Google Scholar 

  • Bläsig J, Herz A, Reinhold K, Zieglgänsberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33:19–38

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Bristow MR, Ginsburg R, Laser JA, McAuley BJ, Winobe W (1984) Tissue response selectivity of calcium antagonists is not due to heterogenity of [3H]-nitrendipine binding sites. Br J Pharmacol 82:309–320

    Google Scholar 

  • Cardenas HL, Ross DH (1976) Calcium depletion of synaptosomes after morphine treatment. Br J Pharmacol 57:521–526

    Google Scholar 

  • Caro G, Barrios M, Baeyens JM (1988) Dose-dependent and stereo-selective antagonism by diltiazem of naloxone-precipitated morphine abstinence after acute morphine-dependence in vivo and in vitro. Life Sci 43:1523–1527

    Google Scholar 

  • Chahl LA (1986) Withdrawal responses of guinea-pig isolated ileum following brief exposure to opiates and opioid peptides. Naunyn Schmiedeberg's Arch Pharmacol 333:387–392

    Google Scholar 

  • Collier HOJ (1980) Cellular site of opiate dependence. Nature 283:625–629

    Google Scholar 

  • Collier HOJ, Francis DL, Henderson G, Schneider C (1974) Quasi morphine-abstinence syndrome. Nature 249:471–473

    Google Scholar 

  • Collier HOJ, Cuthbert NJ, Francis DL (1981) Model of opiate dependence in the guinea-pig isolated ileum. Br J Pharmacol 73:921–932

    Google Scholar 

  • Dolin SJ, Little HJ (1989) Effects of “nitrendipine” on nitrous oxide anesthesia, tolerance, and physical dependence. Anesthesiology 70:91–97

    Google Scholar 

  • Dolin SJ, Halsey MJ, Little HJ (1988a) Effects of the calcium channel activator Bay K 8644 on general anaesthetic potency in mice. Br J Pharmacol 94:413–422

    Google Scholar 

  • Dolin SJ, Patch T, Whittington MA, Siarey RJ, Little HJ (1988b) Evidence for the importance of dihydropyridine-sensitive calcium channels in ethanol tolerance and dependence. Br J Pharmacol 95:877P

  • End DW, Carchman RA, Dewey WL (1981) Interactions of narcotics with synaptosomal calcium transport. Biochem Pharmacol 30:674–676

    Google Scholar 

  • Guerrero-Muñoz F, Cerreta KV, Guerrero ML, Way EL (1979) Effect of morphine on synaptosomal Ca2+ uptake. J Pharmacol Exp Ther 209:132–136

    Google Scholar 

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

    Google Scholar 

  • Hosey HM, Lazdunski M (1988) Calcium channels, molecular pharmacology, structure and regulation. J Membr Biol 104:81–105

    Google Scholar 

  • Little HJ, Dolin SJ, Halsey MJ (1986) Calcium channel antagonists decrease the ethanol withdrawal syndrome. Life Sci 39:2059–2065

    Google Scholar 

  • Littleton JM, Little HJ, Whittington MA (1990) Effects of dihydropyridine calcium channel antagonists in ethanol withdrawal; dose required, stereospecificity and actions of Bay K 8644. Psychopharmacology 100:387–392

    Google Scholar 

  • Luján M, Rodríguez R (1981) Pharmacological characterization of opiate physical dependence in the isolated ileum of the guineapig. Br J Pharmacol 73:859–866

    Google Scholar 

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

    Google Scholar 

  • North RA, Karras PJ (1978) Opiate tolerance and dependence induced in vitro in single myenteric neurones. Nature 272:73–75

    Google Scholar 

  • Nowycky MC, Fox AP, Tsien RW (1985) Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316:440–443

    Google Scholar 

  • Patch T, Little HJ, Siarey RJ, Dolin SJ (1989) Nitrendipine decreases seizure incidence during benzodiazepine withdrawal but not seizures caused by bicuculline. Br J Pharmacol 97:493P

  • Pellegrini-Giampietro DE, Bacciottini L, Carla V, Moroni F (1988) Morphine withdrawal in cortical slices, suppression by Ca++-channel inhibitors of abstinence-induces [3H]-noradrenaline release. Br J Pharmacol 93:535–540

    Google Scholar 

  • Ramkumar V, El-Fakahany EE (1984) Increase in [3H]nitrendipine binding sites in the brain in morphine-tolerante mice. Eur J Pharmacol 102:371–372

    Google Scholar 

  • Ramkumar V, El-Fakahany EE (1988) Prolonged morphine treatment increases rat brain dihydropyridine binding sites, possible involvement in development of morphine dependence. Eur J Pharmacol 146:73–83

    Google Scholar 

  • Sanghvi IS, Gershon S (1976) Morphine dependent rats, blockade of precipitated abstinence by calcium. Life Sci 18:649–654

    Google Scholar 

  • Salvador A, Del Pozo E, Carlos R, Baeyens JM (1988) Differential effects of calcium channel blocking agents on pancuronium and suxamethonium-induced neuromuscular blockade. Br J Anaesth 60:495–499

    Google Scholar 

  • Schramm M, Towart R (1985) Modulation of calcium channel function by drugs. Life Sci 37:1843–1860

    Google Scholar 

  • Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculations with computer programs. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Tsien RW, Lipscombe D, Madison DV, Bley KR, Fox AP (1988) Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci 11:431–437

    Google Scholar 

  • Wagner JA, Guggino SE, Reynolds IJ, Snowman AM, Biswas A, Olivera BM, Snyder SH (1988) Calcium antagonist receptors. Clinical and physiological relevance. Ann NY Acad Sci 522:116–133

    Google Scholar 

  • Zernig G (1990) Widening potential for Ca2+ antagonists, non-L-type Ca2+ channel interaction. TIPS 11:38–44

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Medical School, University of Granada, E-18012, Granada, Spain

    Manuel Barrios & José M. Baeyens

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  1. Manuel Barrios
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  2. José M. Baeyens
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Barrios, M., Baeyens, J.M. Differential effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Psychopharmacology 104, 397–403 (1991). https://doi.org/10.1007/BF02246042

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  • DOI: https://doi.org/10.1007/BF02246042

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