Blockade of Type 5 Metabotropic Glutamate Receptors Prevents Impairment of Motor Behavior Evoked by Intrastriatal Administration of Picrotoxin in Rats

Chronic experiments on Wistar rats showed that only the first of several daily doses of 3 μg of the type 5 metabotropic glutamate receptor antagonist [2-methyl-1,3-thiazol-4-yl]ethynyl-pyridine (MTEP) into the rostral neostriatum decreased performance of a conditioned reflex avoidance response in a shuttle box. During the next two weeks, MTEP microinjections had no effect on the rats’ behavior. MTEP given into the neostriatum along with picrotoxin prevented impairment of active avoidance conditioned reflex performance in the shuttle box and decreased the intensity of motor hyperactivity (“free” activity in an open field and pathological activity in the form of stereotypical hyperkinesia) evoked by this GABAA receptor blocker. The results obtained here do not suggest that the striate type 5 metabotropic glutamate receptor system makes an important contribution to the conditioned avoidance reflex, though they provide evidence that the metabotropic glutamate system is involved in the set of changes in motor behavior initiated by blockade of GABAA receptors. The present data indicate the fundamental possibility that metabotropic glutamate receptors can be used to correct hyperkinetic-type dysfunction of the basal ganglia in humans, i.e., Huntingdon’s chorea, athetosis, etc.