Reduction of striatal dopaminergic neurotransmission elevates striatal proenkephalin mRNA.

Dopamine-containing neurons have been shown to make direct contact with enkephalin-like immunoreactive neurons in the striatum of rat brain (Kubota et al., 1986). Chronic blockade of dopaminergic neurotransmission with the neuroleptic drug haloperidol has been reported to increase the striatal concentration of methionineenkephalin and proenkephalin m R N A (ENK mRNA) (Tang et al., 1983). We investigated whether another manipulation which chronically reduces dopaminergic neurotransmission in the striatum, destruction of nigral dopamine-containing neurons by 6-hydroxydopamine (6-OHDA), would have similar effects. A synthetic, antisense, radiolabeled deoxyribonucleotide probe (30-mer) corresponding to nucleotide positions 7 through 36 of rat ENK m R N A (Howells et al., 1984) was used in the hybridization experiments reported here. Initial characterization of the probe included confirmation of the results of Tang et al. (1983). Under halothane anesthesia rats were implanted with an osmotic minipump (Alza Corp.) which delivered haloperidol (33.7 ~ g / k g per h, s.c., N = 4) or vehicle (3.5 M lactic acid, N = 4). After 5 days the rats were sacrificed for dissection of striata over ice. Total striatal RNA from each rat was isolated, separated on a Northern gel, and blotted to nitrocellulose (Davis et al., 1986). After hybridization with the 32p-5'-end labeled probe, the blot