DIFFERENTIAL-EFFECTS OF CHRONIC DOPAMINE D(1) AND DOPAMINE D(2) RECEPTOR AGONISTS ON ROTATIONAL BEHAVIOR AND DOPAMINE RECEPTOR-BINDING

The effects of chronic continuous and intermittent administration of the dopamine D1 receptor agonist SKF 38393 or the D2 receptor agonist quinpirole on rotational behavior and dopamine receptor binding were examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Continuous and intermittent SKF 38393 both decreased the rotational response to subsequent challenge with SKF 38393. Intermittent SKF 38393 increased quinpirole rotation, while continuous SKF 38393 had no effect. Continuous administration of quinpirole did not affect rotation elicited by either SKF 38393 or quinpirole. Intermittent quinpirole, however, increased both SKF 38393- and quinpirole-induced rotation. Autoradiographic techniques were used to measure D1 receptor binding in striatum and substantia nigra pars reticulata and D2 receptor binding in striatum and nucleus accumbens. Intermittent SKF 38393 reduced D1 receptor B(max) and increased D1 K(d) in the striatum, while both continuous and intermittent treatment with the D1 agonist decreased D1 binding in the substantia nigra pars reticulata. Intermittent quinpirole decreased D1 receptor K(d) in striatum, and continuous quinpirole reduced D1 binding slightly in substantia nigra pars reticulata. Striatal D2 receptor binding was unaffected by treatment with either SKF 38393 or quinpirole. Intermittent SKF 38393 and continuous quinpirole both reversed the lesioned-induced elevation in D2 binding in the nucleus accumbens, while intermittent quinpirole decreased D2 binding in the accumbens on both the intact and denervated sides. Thus, the effects of chronic treatment with D1 and D2 agonists on behavioral responses to D1 and D2 receptor stimulation differed considerably and were dependent on the treatment regimen employed. Changes in D1 receptor-mediated rotational behavior appeared to be associated with alterations in D1 receptor binding in striatum or substantia nigra pars reticulata, while changes in D2-mediated rotation showed no relation to D2 receptor binding in either striatum or nucleus accumbens.