TOPOGRAPHICAL ORGANIZATION OF OPIOID PEPTIDE PRECURSOR GENE-EXPRESSION FOLLOWING REPEATED APOMORPHINE TREATMENT IN THE 6-HYDROXYDOPAMINE-LESIONED RAT

Many studies have previously described changes in preproenkephalin-A ( PPE-A) and preproenkephalin-B (PPE-B) gene expression in the striatum of the 6-hydroxy-dopamine (6-OHDA)-lesioned rat model of Parkinson's d isease (both with or without dopamine replacement treatment). To date, these studies have either taken the striatum as a whole or have focus ed on a single subregion of the striatum. However, the striatum is org anized into anatomically discrete parallel circuits serving different functions (motor, associative, and limbic). We have therefore employed in situ hybridization to examine the detailed topography of changes i n opioid precursor expression following dopamine depletion and subsequ ent treatment with apomorphine (5 mg/kg twice daily for 10 days). In t he untreated 6-OHDA-lesioned striatum PPE-A expression was elevated on ly in the dorsal (sensorimotor) caudate-putamen. Following apomorphine treatment PPE-A mRNA levels were further raised in the sensorimotor s triatum (less than or equal to 77%) and approximately doubled and trip led in the ventral caudate-putamen (associative) and nucleus accumbens (limbic), respectively. These subsequent elevations were mostly restr icted to rostral portions of the striatum. Although unchanged followin g vehicle treatment, PPE-B gene expression in the lesioned caudate-put amen (sensorimotor and associative) was elevated some 30-fold by apomo rphine treatment. A smaller rise (fivefold) was seen in rostral region s of the lesioned nucleus accumbens. Thus, differential regulation of opioid peptide transmission exists in motor, limbic, and associative r egions of the striatum and may contribute to the generation of motor a nd cognitive disturbances following long-term treatment of the dopamin e-depleted striatum. (C) 1998 Academic Press.