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%) and bursty (12%). The switch from simple spiking mode (pacemaker or random) to bursty firing would correspond to an increase in DA release necessary for the performance of a new motor act. As nigral DA cells are impinged upon by a high percentage of GABAergic afferents we blocked striatal GABAergic output neurons by chronic administration into the neostriatum of allyl-glycine, a glutamic acid decarboxylase (GAD) inhibitor. After treatment, rats presented hyperkinesia and hypertonia on the injected side and recordings showed a drastic change in the percentage distribution of nigral DA cell discharge patterns; 85% were 'random', 12% 'pacemaker' and 3% bursty. Such a disturbance, by impeding adapted DA release, may account for the hyperkinetic and dystonic disorders observed.