Electrical stimulation of the nigrostriatal pathway after HA-966 block of triatal dopamine release.

Striatal dopamine (DA) of rats increased twofold 1 h after blockade of DA release by either an electrolytic lesion of the substantia nigra (SN) or systemic administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966). If the treatments were combined, no further increase was observed. The decrease in DA induced by alpha-methyl-p-tyrosine (alphaMT) in otherwise untreated animals was not enhanced by a 20 min electrical stimulation of nigrostriatal fibres. If, however, in addition to synthesis blockade by alphaMT, DA release was interrupted by a lesion of the SN and/or by HA-966, electrical stimulation caused a significant decrease in striatal DA. It is assumed that HA-966 exerts its action in the dopaminergic nigrostriatal system by way of blockade of the nerve impulse flow at the level of the SN.