The role of GABA in the substantia nigra

Abstract

STRIATONIGRAL GABAergic fibres are widely believed to exert a tonic inhibitory influence on the dopamine (DA)-containing cells of the substantia nigra (SN), and contraversive and ipsiversive circling behaviour can be explained in terms of a greater or lesser activity of the dopaminergic neurones, respectively^1,2. However, the blockade of γ-aminobutyric acid (GABA) receptors with intranigral picrotoxin occasionally stimulates rats to turn ipsiversively^3,4, rather than evoking the more commonly observed response in the opposite direction⁵. Similarly, injections of GABA agonists into the SN sometimes trigger an atypical contraversive turning syndrome^3,4,6,7. We describe here a study which sought to reconcile these paradoxical phenomena by investigating the effects on circling behaviour of decreasing the influence of GABA within the SN with picrotoxin, and of potentiating the action of GABA with cis-1,3-aminocyclohexane carboxylic acid (ACHC)⁸, a neuronal GABA uptake inhibitor. We show that the same drugs are capable of producing opposite turning responses when injected into the rostral and caudal parts of the SN. Moreover, behaviour patterns influenced by the anterior SN are accompanied by significant changes in homovanillic acid (HVA) levels in the striatum and require an intact DA system, whereas turning responses initiated by caudal drug injections are apparently not mediated by the dopaminergic nigrostriatal pathway.