The role of GABA receptors in the control of nigrostriatal dopaminergic neurons: dual-probe microdialysis study in awake rats

Abstract

A microdialysis probe implanted into the substantia nigra was used to infuse gamma-aminobutyric acid-ergic (GABAergic) compounds onto cell bodies/dendrites of dopaminergic neurons, while a second microdialysis probe was used to record the extracellular concentrations of dopamine and 3,4-dihydroxy-phenylacetic acid (DOPAC) in the ipsilateral striatum. The GABAA receptor agonist muscimol (10 mumol/l) increased the release of dopamine in the ipsilateral striatum to 120% of the control values. The GABAB receptor agonist, (Z)-3[(aminoiminomethyl)-thiol]-prop-2- enoic acid (500 mumol/l), was without effect. Infusion of the GABAA receptor antagonists, bicuculline (50 mumol/l) and picrotoxin (50 mumol/l), stimulated the release of dopamine in the ipsilateral striatum to 160 and 130% of the controls, respectively. The GABAB receptor agonist, baclofen (10 and 50 mumol/l), strongly inhibited the release of striatal dopamine, whereas infusion of the GABAB receptor antagonist, 2-hydroxy-saclofen (100 mumol/l), was without effect. The results indicate that, in the substantia nigra, GABAA as well as GABAB receptors participate in controlling the activity of dopaminergic neurons.