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

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 acti ve agonist of group II mGlu receptors. After peripheral administration, LY 354740 produced anxiolytic-Iike effects in the conflict drinking test in ra ts and a four-plate test in mice. It was also found that LY 354740 decrease d spontaneous locomotor activity in mice, but did not disturb motor coordin ation. In behavioural models of depression including the despair test and a tail suspension test, LY 354740 did not produce antidepressant-like effect s. LY 354740 inhibited the naloxone-induced symptoms of morphine withdrawal in morphine-dependent mice. The above results indicate that agonists of gr oup 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 ident ified and the mechanism of both the above described effects remains to be e lucidated. (C) 1999 Elsevier Science Ltd. All rights reserved.