NEUROCHEMICAL CORRELATES OF BEHAVIORAL SENSITIZATION FOLLOWING REPEATED APOMORPHINE TREATMENT - ASSESSMENT OF THE ROLE OF D(1)-DOPAMINE RECEPTOR STIMULATION

Previous research has revealed a role of repeated D1 dopamine receptor stimulation in the development of behavioral sensitization to the D1/ D2 agonist apomorphine. The present experiments assessed the role of r epeated D1 receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D1 stimulation on dopamine synthesis, rats were injected with the D1 ago nist SKF 38393 (8 mg/kg), followed by an injection with the 3,4-dihydr oxyphenylalanine (DOPA) decarboxylase inhibitor, NSD-1015. DOPA accumu lation, assessed in striatal, nucleus accumbens-olfactory tubercle (NA OT), and ventral mesencephalon (VM) tissue samples, was not affected b y acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D1 agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demons trated a progressive increase in the apomorphine-treated rats, but not the SKF 38393-treated rats, across the 10 days. On day 11, all rats w ere injected with NSD-1015 for measurement of DOPA accumulation. Dopam ine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in eithe r a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue le vels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and [H-3]SCH 23390 binding to D1 receptors were measured in rats treated with 10 da ily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/ kg). In the striatum and NAOT, none of the repeated drug treatments ha d an effect on DOPAC or dopamine levels. In the VM, DOPAC levels were enhanced following repeated apomorphine, but not repeated SKF 38393, w hereas dopamine levels were not affected by either drug treatment. D1 binding was not altered by the repeated drug treatments. Since repeate d D1 stimulation by SKF 38393 did not produce the same alterations in dopamine synthesis and DOPAC levels as repeated apomorphine, the neuro chemical effects accompanying locomotor sensitization to apomorphine p robably are not mediated by D1 receptors.