DOPAMINERGIC REGULATION OF GLUTAMIC-ACID DECARBOXYLASE MESSENGER-RNA EXPRESSION AND GABA RELEASE IN THE STRIATUM - A REVIEW

1. The majority of neurons in the striatum (caudate-putamen, dorsal st riatum; nucleus accumbens, ventral striatum) and in striatal projectio n regions (the pallidum, the entopeduncular nucleus and substantia nig ra reticulata) use gamma-aminobuturic acid (GABA) as transmitter and e xpress glutamic acid decarboxylase (GAD; rate limiting enzyme) in the synthesis of GABA. GABA is the major inhibitory transmitter in the mam mlian brain. 2. GAD in brain is present as two isoenzymes, GAD65 and G AD67. GAD65 is largely present as an inactive apoenzyme, which can be induced by nerve activity, while most GAD67 is present as a pyridoxal phosphate-bound permanently active holoenzyme. Thus GAD65 and GAD67 se em to provide a dual system for the control of neuronal GABA synthesis . 3. GAD mRNA expression can be visualised and quantified using in sit u hybridisation, and GABA release can be quantified using in vivo micr odialysis. 4. Different populations of GABA neurons can be distinguish ed in both dorsal and ventral striatum as well as in other parts of th e basal ganglia. 5. Inhibition of dopaminergic transmission in the str iatum by lesion of dopamine neurons or by neuroleptic treatment is fol lowed by an increased release of GABA and increased expression of GAD6 7 mRNA in a subpopulation of striatal medium-sized neurons which proje ct to the globus pallidus, and increased striatal GAD enzyme activity. 6. Increased dopaminergic transmission by repeated but not single dos es of amphetamine is followed by decreased striatal GABA release and d ecreased GAD67 mRNA expression in a subpopulation of medium-sized neur ons in the striatum. 7. Two populations of medium-sized GABA neurons i n the striatum seem to be under tonic dopaminergic influence. The majo rity of these GABA neurons are under inhibitory influence, whereas a s mall number seem to be stimulated by dopamine. 8. Specific changes in activity in subpopulations of striatal GABA neurons probably mediate t he dopamine-dependent hypokinetic syndrome seen in Parkinson's disease and following neuroleptic treatment.