Elsevier

Brain Research

Volume 652, Issue 1, 25 July 1994, Pages 1-8
Brain Research

Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644 and nimodipine

https://doi.org/10.1016/0006-8993(94)90310-7Get rights and content

Abstract

The aim of the present work was to clarify the role of calcium influx through L-type calcium channels in the rewarding and analgesic effects of morphine. Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium agonist and antagonist, respectively, on the analgesic and rewarding effects of morphine in mice were studied. Morphine-induced analgesia was measured with the aid of writhing test, hot plate test and tail clip test. The rewarding properties of morphine were studied using i.v. self-administration in drug-naive mice. Bay K-8644 potentiated morphine-induced analgesia in all the tests. The influence of nimodipine on morphine analgesia was more complicated and depended on those of morphine and test used. In self-administration experiments morphine exhibited the bell-shaped concentration-response curve. Bay K-8644 produced a shift of the curve to the left, while nimodiine had the oposite action indicating, respectively, facilitating and inhibitory influence on morphine rewarding effect. It is concluded that nimodipine exhibites partial antagonistic properties towards the rewarding action of morphine and slightly potentiates morphine-induced analgesia while Bay K-8644 increases either the rewarding or the analgesic effects of morphine.

Reference (44)

  • SmithF.L. et al.

    Endogenous dynorphin modulates calcium-mediated antinociception in mice

    Pharmacol. Biochem. Behav.

    (1993)
  • AttaliB. et al.

    Kappa-opiate agonists inhibit calcium influx in rat spinal cord-dorsal root ganglion cocultures

    J. Biol. Chem.

    (1989)
  • BechemM. et al.

    Calcium agonist: new sensitive probes for Ca2+ channels

    Trends Pharmacol. Sci.

    (1988)
  • BenekikG. et al.

    Potentiation of thermoregulatory and analgesic effects of morphine by calcium channel antagonists

    Pharmacol. Res. Commun.

    (1984)
  • ChapmanD.B. et al.

    Metal ion interactions with opiates

    Annu. Rev. Pharmacol. Toxicol.

    (1980)
  • Del PozoE. et al.

    Analgesic effects of several calcium channel blockers in mice

    Eur. J. Pharmacol.

    (1987)
  • DierssenM. et al.

    Calcium channel modulation by dihydropyridines modifies sufentanil-induced antinociception in acute and tolerant conditions

    Naunyn-Schmiedeberg's Arch. Pharmacol.

    (1990)
  • DierssenM. et al.

    Calcium channel modulation by dihydropyridines modifies sufentanil-induced respiratory depression in cats

    Eur. J. Pharmacol.

    (1991)
  • GlossmanH. et al.

    Non L-type Ca2+ channel linked receptors for 1,4-dihydropyridines and phenylalkylamines

  • GovoniS. et al.

    Calcium antagonists inhibit Met-enkephalin immunoreactive material release: in vivo and ex vivo experiments

    J. Neural Transm.

    (1990)
  • Guerrero-MunozF. et al.

    Effects of morphine on synaptosomal Ca2+ uptake

    J. Pharmacol. Exp. Ther.

    (1979)
  • HarrisR.A. et al.

    Effects of different cations, cation chelators and an ionophore on morphine analgesia and tolerance

    J. Pharmacol. Exp. Ther.

    (1975)
  • Cited by (27)

    • Effects of calcium channel antagonists on the motivational effects of nicotine and morphine in conditioned place aversion paradigm

      2012, Behavioural Brain Research
      Citation Excerpt :

      Given evidence such as this, an increased calcium influx through up-regulated L-type VDCCs may be involved in the development of opioid dependence causing the release of neurotransmitters important for this kind of addiction (i.e., dopamine, glutamate). Many studies have shown that VDCCs participate in morphine-induced analgesia [73,74] and other dependence-producing effects of opioid agonists [22,28]. In accordance, phosphorylation by kinases as cAMPdependent protein kinase (PKA), essential for LTP induction, has been shown to positively affect ion gating [75].

    • BAY-K 8644

      2009, xPharm: The Comprehensive Pharmacology Reference
    View all citing articles on Scopus
    View full text