Differential effects of chronic dopamine D 1 and D 2 receptor agonists on rotational behavior and dopamine receptor binding

Abstract

The effects of chronic continuous and intermittent administration of the dopamine D 1 receptor agonist SKF 38393 or the D 2 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 D 1 receptor binding in striatum and substantia nigra pars reticulata and D 2 receptor binding in striatum and nucleus accumbens. Intermittent SKF 38393 reduced D 1 receptor B max and increased D 1 K d in the striatum, while both continuous and intermittent treatment with the D 1 agonist decreased D 1 binding in the substantia nigra pars reticula. Intermittent quinpirole decreased D 1 receptor K d in striatum, and continuous quinpirole reduced D 1 binding slightly in substantia nigra pars reticulata. Striatal D 2 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 D 2 binding in the nucleus accumbens, while intermittent quinpirole decreased D 2 binding in the accumbens on both the intact and denervated sides. Thus, the effects of chronic treatment with D 1 and D 2 agonists on behavioral responses to D 1 and D 2 receptor stimulation differed considerably and were dependent on the treatment regimen employed. Changes in D 1 receptor-mediated rotational behavior appeared to be associated with alterations in D 1 receptor binding in striatum or substantia nigra pars reticulata, while changes in D 2-mediated rotation showed no relation to D 2 receptor binding in either striatum or nucleus accumbens.