Metabotropic glutamate receptor 2/3-dependent long-term depression in the nucleus accumbens is blocked in morphine withdrawn mice

Eur J Neurosci. 2002 Dec;16(11):2231-5. doi: 10.1046/j.1460-9568.2002.02273.x.

Abstract

The nucleus accumbens (NAc) plays a crucial role in addiction. We have recently shown that activation of presynaptic metabotropic glutamate 2/3 receptors (mGlu2/3) induces long-term depression (LTD) at glutamatergic synapses in the mouse nucleus accumbens (NAc) through the long lasting inhibition of P/Q-type Ca2+ channels and the cAMP/protein kinase A (PKA) pathway. Because presynaptic mGlu2/3 functions are augmented in the ventral tegmental area of morphine-withdrawn rats, we have evaluated the consequences of opiate treatment on mGlu2/3 LTD at prelimbic NAc glutamatergic synapses. Here we report that mGlu2/3 LTD is abolished after 1 week of withdrawal from chronic morphine treatment; in the morphine-withdrawn group LTD measured 5.99 +/- 4.84% (P < 0.05) compared with 21.13 +/- 5.42% in the sham group. In contrast, chronic morphine treatment did not alter the mechanisms normally underlying mGlu2/3 LTD, such as the cAMP/PKA pathway or P/Q-type Ca2+ channels. This study shows that one long-term consequence of morphine treatment is an alteration of synaptic plasticity at glutamatergic synapses in the NAc. Considering that mGlu2/3 agonists (e.g. LY-354740 used in the present study to induce LTD) reduce behavioural symptoms of morphine withdrawal, these findings could be important in the understanding of the cellular events underlying the dependence-inducing properties of opiates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / drug effects
  • Adenylyl Cyclases / metabolism
  • Animals
  • Cyclic AMP / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Long-Term Synaptic Depression / drug effects*
  • Long-Term Synaptic Depression / physiology
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology*
  • Morphine Dependence / metabolism*
  • Morphine Dependence / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Purinergic P1 Receptor Antagonists
  • Receptors, Metabotropic Glutamate / drug effects*
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, Purinergic P1 / metabolism
  • Substance Withdrawal Syndrome / metabolism*
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Excitatory Amino Acid Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptors, Metabotropic Glutamate
  • Receptors, Purinergic P1
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Morphine
  • Cyclic AMP
  • Adenylyl Cyclases