CHRONIC GAMMA-BUTYROLACTONE (GBL) TREATMENT - POTENTIAL MODEL OF DOPAMINE HYPOACTIVITY

Gamma-butyrolactone (GBL) is a general depressant of the central nervous system which has proved to be a useful tool for studying the dopamine system. Administration of GBL to rats produces an acute blockade of impulse flow in the nigro-neostriatal dopaminergic pathway, in effect causing a reversible pharmacological lesion of this pathway. In this study the effects of chronic treatment of rats with GBL were examined. After 1 month of chronic treatment, the average firing rates of A9 dopamine cells were significantly depressed below those of control rats. Striatal dihtdroxyphenylacetic acid levels were also depressed, while striatal dopamine levels and in vivo tyrosine hydroxylase activity (measured by dopa accumulation after inhibition of dopa decarboxylase) were at control values. Tolerance developed to the behavioral effects of GBL (measured by duration of loss of righting reflex after a challenge dose). The tolerance was partially overcome by increasing the amount of the challenge dose. Tolerance also developed to the ability of a challenge dose to elicit increased dopamine synthesis. However, synthesis responded normally to mechanical lesion and electrical stimulation of the dopamine fibers. Both post-and presynaptic dopamine receptors became supersensitive after chronic treatment with GBL. These findings suggest that chronic treatment with GBL may provide a model system for studying the effects of partial deprivation of dopaminergic activity. © 1979 Springer-Verlag.