Potential anti-anxiety, anti-addictive effects of LY 354740, a selective group II glutamate metabotropic receptors agonist in animal models

Neuropharmacology. 1999 Dec;38(12):1831-9. doi: 10.1016/s0028-3908(99)00066-0.


Despite there being a lot of biochemical data about metabotropic glutamate (mGlu) receptors, our knowledge of the behavioural effects of mGlu receptor agonists/antagonists is still inadequate. LY 354740 is a systemically active agonist of group II mGlu receptors. After peripheral administration, LY 354740 produced anxiolytic-like effects in the conflict drinking test in rats and a four-plate test in mice. It was also found that LY 354740 decreased spontaneous locomotor activity in mice, but did not disturb motor coordination. In behavioural models of depression including the despair test and a tail suspension test, LY 354740 did not produce antidepressant-like effects. LY 354740 inhibited the naloxone-induced symptoms of morphine withdrawal in morphine-dependent mice. The above results indicate that agonists of group II mGlu receptors may play a role in the therapy of anxiety and/or drug-dependence states. The brain sites of action of LY 354740 need to be identified and the mechanism of both the above described effects remains to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / therapeutic use*
  • Behavior, Animal / drug effects*
  • Bridged Bicyclo Compounds / therapeutic use*
  • Conflict, Psychological
  • Drinking / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / adverse effects
  • Motor Activity / drug effects*
  • Narcotics / adverse effects
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists*
  • Substance Withdrawal Syndrome / drug therapy


  • Anti-Anxiety Agents
  • Bridged Bicyclo Compounds
  • Narcotics
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Morphine
  • eglumetad