Apomorphine-induced rotation in the unilateral 6-ohda-lesioned rat: Relationship to changes in striatal adenylate cyclase activity and 3H-spiperone binding

Abstract

Rotational responses to apomorphine in rats with unilateral 6-hydroxydopamine lesions were significantly correlated with increases in 3H-spiperone binding but not with increases in DA-stimulated adenylate cyclase activity in lesioned striata. This behavioural index of DA receptor supersensitivity may be mediated by proliferation of those DA receptors that bind 3H-spiperone but are not linked to adenylate cyclase. Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopamine (DA) pathway exhibit contralateral rotational behaviour when challenged with DA agonists Such as apomorphine. This behavioural supersensitivity has been shown to be accompanied by an increase in striatal 3H-haloperidol binding sites (Creese et al., 1977; Seeman et al., 1978). However, studies of the activity of striatal DA-sensitive adenylate cyclase (AC) after such lesions have produced conflicting results (Iversen, 1975; Krueger et al., 1976). While both of these biochemical measures have been proposed as in vitro indices of the DA receptor, recent data suggest they may reflect different types of receptor (Kebabian and Calne, 1979)- The behavioural significance of these two in vitro measures is at present unclear. In the present study we have used rotational response to apomorphine as a behavioural index of DA receptor supersensitivity after unilateral 6-OHDA lesion. In an attempt to determine the functional significance of the in vitro measures of DA receptor sites we have correlated changes in both DA-stimulated AC activity and 3H-spiperone binding in lesioned striata with their associated rotational responses to apomorphine.