Irreversible blockade of D2 dopamine receptors by fluphenazine-N-mustard increases glutamic acid decarboxylase mRNA in rat striatum.

The influence of dopaminergic activity on the function of GABAergic neurons in striatum was examined by administering rats the irreversible D2 dopamine receptor antagonist, fluphenazine-N-mustard (FNM), and determining the level of glutamic acid decarboxylase (GAD) mRNA in striatum. Rats were given either an acute single injection or chronic daily injections of FNM (20 mumol/kg, i.p.) for 6 days. The level of GAD mRNA in striatum was determined by in situ hybridization histochemistry. The results showed that acute treatment with FNM failed to significantly change striatal GAD mRNA. However, chronic FNM treatment significantly increased in the level of striatal GAD mRNA. These results demonstrate that irreversible blockade of D2 dopamine receptors increases the expression of GAD mRNA in rat striatum.