DOPAMINE-GLUTAMATE INTERACTIONS IN THE BASAL GANGLIA

In an attempt to formulate a working hypothesis of basal-ganglia funct ions, arguments are considered suggesting that the basal ganglia are i nvolved in a process of response selection i.e. in the facilitation of ''wanted'' and in the suppression of ''unwanted'' behaviour. The meso -accumbal dopamine-system is considered to mediate natural and drug-in duced reward and sensitization. The meso-striatal dopamine-system seem s to fulfill similar funcions: It may mediate reinforcement which stre ngthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subth alamic neurons is critically involved in basal ganglia funcions and dy sfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an es sential factor in the plasticity response of the basal-ganglia. Howeve r, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant-nor morphine-induced day to day incre ase (sensitization) of locomotion. Also the day to day increase of hal operidol-induced catalepsy was not prevented by MK-801.