D1 priming enhances both D1- and D2-mediated rotational behavior and striatal Fos expression in 6-hydroxydopamine lesioned rats

Abstract

Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions exhibit behavioral sensitization upon repeated treatment with dopamine agonists, a phenomenon called 'priming'. We examined the effectiveness of priming with D1 or D2 agonists on rotational behavior and striatal Fos expression following challenge with D1 or D2 agonists. Twenty-one days post-lesion, rats received three priming injections, spaced 3-6days apart, with water, D1 agonist SKF38393 (10mg/kg) or D2 agonist quinpirole (1mg/kg). One week later, 6-OHDA rats were challenged with water, SKF38393 (1 or 10mg/kg) or quinpirole (0.25mg/kg). 6-OHDA rats challenged with SKF38393 (1mg/kg) showed no contralateral rotational behavior, but robust striatal Fos expression in D1-primed animals. Challenge with SKF38393 (10mg/kg) led to pronounced contralateral rotational behavior and striatal Fos expression in all priming groups - with the largest behavioral response in D1- and D2-primed rats. Quinpirole challenge (0.25mg/kg) led to robust contralateral rotational behavior and striatal Fos expression in D1-primed animals, but only mild rotational behavior and baseline levels of striatal Fos expression in D2-primed animals. These data suggest that D1- or D2-priming enhances rotational behavior following challenge with D1 or D2 agonist, but only D1-priming enhances D1- and D2-mediated striatal Fos expression in 6-OHDA rats.