ENHANCEMENT OF THE BEHAVIORAL-RESPONSE TO APOMORPHINE ADMINISTRATION FOLLOWING REPEATED TREATMENT IN THE 6-HYDROXYDOPAMINE-LESIONED RAT IS TEMPORALLY CORRELATED WITH A RISE IN STRIATAL PREPROENKEPHALIN-B, BUT NOT PREPROENKEPHALIN-A, GENE-EXPRESSION

Repeated dopamine receptor stimulation in the B-hydroxydopamine(6-OHDA )-lesioned rat produces a marked enhancement in the behavioral respons e to a given dose of dopamine agonist, Such treatment also increases t he synthesis of preproenkephalin-B (PPE-B) throughout the striatum and preproenkephalin-A (PPE-A) rostrally, To examine the relationship bet ween these changes, 6-OHDA-lesioned rats were treated with apomorphine (5 mg/kg) twice-daily, Between 0.5 and 7 days treatment, behavior was monitored and the levels of PPE-A and PPE-B mRNA were determined by i n situ hybridization, A single injection of apomorphine induced a well -known rotational response contraversive to the lesion (314 +/- 22 rot ations h(-1)), However, with repeated injection, the response to apomo rphine was markedly enhanced, being significantly higher on Days 3 (70 4 +/- 60 rotations h(-1)), 5 (1354 +/- 104 rotations h(-1)), and 7 (16 80 +/- 117 rotations h(-1)), In the lesioned caudate-putamen, but not in the nucleus accumbens, PPE-B expression rose in a manner that was t emporally correlated with the enhanced locomotor response to apomorphi ne, PPE-A expression in the lesioned striatum, significantly increased only after 7 days treatment, did not correlate with the behavioral re sponse, In conclusion, PPE-B may contribute to the development of beha vioral supersensitivity following repeated dopamine-replacement therap y in animal models of Parkinson's disease. (C) 1997 Academic Press.