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 6-hydroxydopamine (6-OHDA)-lesioned rat produces a marked enhancement in the behavioral response to a given dose of dopamine agonist. Such treatment also increases the synthesis of preproenkephalin-B (PPE-B) throughout the striatum and preproenkephalin-A (PPE-A) rostrally. To examine the relationship between 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 in situ hybridization. A single injection of apomorphine induced a well-known rotational response contraversive to the lesion (314 +/- 22 rotations h-1). However, with repeated injection, the response to apomorphine was markedly enhanced, being significantly higher on Days 3 (704 +/- 60 rotations h-1), 5 (1354 +/- 104 rotations h-1), and 7 (1680 +/- 117 rotations h-1). In the lesioned caudate-putamen, but not in the nucleus accumbens, PPE-B expression rose in a manner that was temporally correlated with the enhanced locomotor response to apomorphine. PPE-A expression in the lesioned striatum, significantly increased only after 7 days treatment, did not correlate with the behavioral response. In conclusion, PPE-B may contribute to the development of behavioral supersensitivity following repeated dopamine-replacement therapy in animal models of Parkinson's disease.