On a Prime Role for Newly Synthesized Dopamine in Striatal Function

Rats were given either the tyrosine hydroxylase inhibitor, alpha-methyltyrosine (alphaMT), in doses of 10 or 250 mg/kg or the neuroleptic, haloperidol (0.25 mg/kg). Other rats received both drugs (haloperidol 30 min after alphaMT). This dose of haloperidol alone caused only a slight, gradually developing catalepsy, while alphaMT alone caused none. The combination quickly caused a strong catalepsy. Striatal dopamine (DA) stores were only minimally depleted at the time of catalepsy potentiation. Th e marked elevation of striatal homovanilluc acid concentration seen after haloperidol administration was greatly inhibited by alphaMT pretreatment. It is concluded that the marked potentiation of haloperidol-induced catalepsy by alpha MT is related to the absence of newly synthesized DA rather than to an exhausted main DA pool and that newly synthesized DA has a greater role in striatal function than does DA of the main striatal storage pool.