PSYCHOPHARMACOLOGICAL EVIDENCE FOR A ROLE OF THE ATP-SENSITIVE POTASSIUM CHANNEL IN THE SUBSTANTIA-NIGRA OF THE RAT

Recent evidence suggests that an ATP-sensitive potassium channel is present in the brain. From ligand binding studies it has been inferred that this relatively unfamiliar channel is particularly densely distributed in areas associated with motor control. The aim of this study was thus to examine whether pharmacological agents, specific for the ATP-sensitive channel in other tissues, had effects on a particular motor behaviour associated with the substantia nigra: the effects of microinfusion into the substantia nigra of diverse potassium channel blocking agents were examined on the initiation of circling behaviour in the normal rat. Application of tolbutamide and quinine, but not tetraethylammonium, caused circling behaviour in the presence of a systemically administered challenge of amphetamine. However, in the case of application of tolbutamide, the direction of circling was dependent on whether the site of infusion was in the pars compacta or pars reticulata. On the other hand, the effects of quinine were the same, irrespective of site application within the substantia nigra, i.e. in the same direction, as seen after injection of tolbutamide into the pars compacta. Quinine and tolbutamide are different chemical species which both, unlike tetraethylammonium, principally block the ATP-sensitive potassium channel. It therefore seems that an ATP-sensitive potassium channel in the pars compacta cells of the substantia nigra could play a selective role in modifying the net activity of the nigrostriatal pathway and hence the control of movement.