CHRONIC ADMINISTRATION OF DL-ALLYL-GLYCINE INTO THE NEOSTRIATUM, DISORGANISES THE FIRING MODES OF THE NIGRAL DOPAMINERGIC-NEURONS IN THE RAT

Nigral dopaminergic (DA) neurons have been reported to fire according to three modes: very regular (pacemaker 42%) irregular (random 46%) an d bursty (12%). The switch from simple spiking mode (pacemaker or rand om) to bursty firing would correspond to an increase in DA release nec essary for the performance of a new motor act. As nigral DA cells are impinged upon by a high percentage of GABAergic afferents we blocked s triatal GABAergic output neurons by chronic administration into the ne ostriatum of allyl-glycine, a glutamic acid decarboxylase (GAD) inhibi tor. After treatment, rats presented hyperkinesia and hypertonia on th e injected side and recordings showed a drastic change in the percenta ge distribution of nigral DA cell discharge patterns; 85% were 'random ', 12% 'pacemaker' and 3% bursty. Such a disturbance, by impeding adap ted DA release, may account for the hyperkinetic and dystonic disorder s observed. (C) 1997 Elsevier Science Ireland Ltd.