The effects of elevating gamma-amino butyrate content in the substantia nigra on the behaviour of rats.

Gabaculine, a specific inhibitor of GABA transaminase, was injected bilaterally into the substantia nigra of rats. One day after injection, GABA was increased 11-fold in the nigra, 6-fold in thalamus and pons-medulla, and 2-fold in pallidum. 5 h after operation, rats showed continuous sniffing and head movement. This behaviour was blocked by a small dose of picrotoxin injected bilaterally into the nigra, but haloperidol (i.p.) was less effective. One day after injection, rats showed high ambulation and this ambulation was blocked by high doses of picrotoxin. On the second day, GABA contents in all regions were less than twice the control level and behaviour had returned to normal. Rats with gabaculine injected into the pallidum or medulla did not show changes of behaviour as seen in rats with injections into the substantia nigra at any of the times. Striatum dopamine turnover was slightly but significantly decreased at 5 h but not at 24 h after intra-nigral injection with gabaculine. The results suggest that gabaculine-induced sniffing and head movement were mediated by nigral GABAergic synapses and were independent of any dopaminergic system, and that the high ambulation at 24 h after operation may have been due to a non-specific effect of abnormal GABA elevation in thalamus and/or nigra.