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 t he dopamine D1 receptor agonist SKF 38393 or the D2 receptor agonist q uinpirole on rotational behavior and dopamine receptor binding were ex amined in rats with a unilateral 6-hydroxydopamine lesion of the nigro striatal pathway. Continuous and intermittent SKF 38393 both decreased the rotational response to subsequent challenge with SKF 38393. Inter mittent SKF 38393 increased quinpirole rotation, while continuous SKF 38393 had no effect. Continuous administration of quinpirole did not a ffect rotation elicited by either SKF 38393 or quinpirole. Intermitten t quinpirole, however, increased both SKF 38393- and quinpirole-induce d rotation. Autoradiographic techniques were used to measure D1 recept or binding in striatum and substantia nigra pars reticulata and D2 rec eptor binding in striatum and nucleus accumbens. Intermittent SKF 3839 3 reduced D1 receptor B(max) and increased D1 K(d) in the striatum, wh ile both continuous and intermittent treatment with the D1 agonist dec reased D1 binding in the substantia nigra pars reticulata. Intermitten t quinpirole decreased D1 receptor K(d) in striatum, and continuous qu inpirole reduced D1 binding slightly in substantia nigra pars reticula ta. Striatal D2 receptor binding was unaffected by treatment with eith er SKF 38393 or quinpirole. Intermittent SKF 38393 and continuous quin pirole both reversed the lesioned-induced elevation in D2 binding in t he nucleus accumbens, while intermittent quinpirole decreased D2 bindi ng in the accumbens on both the intact and denervated sides. Thus, the effects of chronic treatment with D1 and D2 agonists on behavioral re sponses to D1 and D2 receptor stimulation differed considerably and we re dependent on the treatment regimen employed. Changes in D1 receptor -mediated rotational behavior appeared to be associated with alteratio ns in D1 receptor binding in striatum or substantia nigra pars reticul ata, while changes in D2-mediated rotation showed no relation to D2 re ceptor binding in either striatum or nucleus accumbens.