Elsevier

Brain Research

Volume 718, Issues 1–2, 29 April 1996, Pages 203-206
Brain Research

Opioid receptors in the ventral tegmental area contribute to stress-induced analgesia in the formalin test for tonic pain

https://doi.org/10.1016/0006-8993(96)00121-7Get rights and content

Abstract

Exposure to stress can induce analgesia in the formalin test for tonic pain. Here, we report that blockade of opioid receptors by bilateral infusions of naltrexone methylbromide (NMB) (0.1 μg/0.5 μl/side) in the ventral tegmental area (VTA) in the midbrain can reduce stress-induced analgesia in this test. These findings indicate that endogeneous opioids act in the VTA to mediate stress-induced analgesia in tonic pain.

References (42)

  • FanselowM.S. et al.

    Conditioned fear-induced opiate analgesia on the formalin test: evidence for two aversive motivational systems

    Learn. Motiv.

    (1982)
  • FanselowM.S. et al.

    Delta opioid antagonist, 16-Me cyprenorphine, selectively attenuates conditional fear- and DPDPE-induced analgesia in the formalin test

    Pharmacol. Biochem. Behav.

    (1989)
  • HelmstetterF.J. et al.

    Effects of naltrexone on learning and performance of conditional fear-induced freezing and opioid analgesia

    Physiol. Behav.

    (1987)
  • JohnsonR.P. et al.

    A topographic localization of enkephalin on the dopamine neurons of the rat substantia nigra and ventral tegmental area demonstrated by combined histofluorescence-immunocytochemistry

    Brain Res.

    (1980)
  • JoyceE.M. et al.

    The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous activity in the rat

    Neurosci. Lett.

    (1979)
  • JoyceE.M. et al.

    The behavioral effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus

    Brain Res.

    (1981)
  • KalivasP.W. et al.

    Enkephalin release into the ventral tegmental area in response stress: modulation of mesocorticolimbic dopamine

    Brain Res.

    (1987)
  • LewisJ.W. et al.

    Opioid and non-opioid mechanisms of footshock-induced analgesia: role of the spinal dorsolateral funiculus

    Brain Res.

    (1983)
  • MaierS.F. et al.

    The formalin test and the opioid nature of stress-induced analgesia

    Behav. Neural Biol.

    (1984)
  • MillerJ.D. et al.

    Naloxone antagonism of stress-induced augmention of frontal cortex dopamine metabolism

    Eur. J. Pharmacol.

    (1984)
  • NaranjoJ.R. et al.

    Locomotor activation induced in rodents by substance P and analogues

    Neuropharmacology

    (1984)
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      The interaction between opioid and dopaminergic pathways in pain modulation and nociception has been discussed by several authors: dopaminergic receptor antagonists attenuate nociception induced by morphine in ventral tegmental area (Altier and Stewart, 1998); systemic administration of morphine alters dopamine spinal levels (Weilfugazza and Godefroy, 1991) and this raise was not influenced by dopaminergic antagonists (Millan, 2002); depletion of the gene encoding D2 receptors or administration of an antisense probe directed against D2 receptors potentiated antinociception elicited by μ and κ-opioid agonists (King et al., 2001); D2 agonists enhance opioid antinociception (Kamei and Saitoh, 1996; Millan, 2002; Zarrindast et al., 1999). Furthermore, Altier and Stewart (1993, 1996) demonstrated that the ventral tegmental area is associated with opioid and dopaminergic nociception and Ambrose and co-workers suggested the co-existence between opioid and dopaminergic receptors in striatal neurons (Ambrose et al., 2004, 2006). Dorsolateral striatum D2 receptors, but not D1, are involved in the modulation of persistent nociception (Magnusson and Fisher, 2000).

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