Metabotropic glutamate receptor activation and blockade: their role in long-term potentiation, learning and neurotoxicity

Metabotropic glutamate receptors represent a fairly recent addition to the family of glutamate receptors. These receptors have the distinguishing feat ure of bring coupled to G-proteins rather than ion channels and they appear to have a variety of functional characteristics. These receptors play a vi tal role, for example, in the induction and maintenance of long-term potent iation, the most popular current model of the biological correlates of lear ning and memory. Blockade of metabotropic glutamate receptors prevents long -term potentiation induction and learning in a variety of tasks in differen t species. Chronic metabotropic glutamate receptor activation is also assoc iated with neurodegeneration and selective neuronal loss when agonists of t hese receptors are injected in high concentrations directly into the brain. Metabotropic glutamate receptors also play a role in the normal developmen t of the nervous system and these sites within the central nervous system o ffer possible routes for drug therapies; selective receptor antagonists, fo r example, may prove to have the very desirable feature of endowing neuropr otection during ischaemic episodes whilst allowing normal excitatory neurot ransmission to occur. (C) 1999 Elsevier Science Ltd. All rights reserved.