Behavioral activity of some novel aporphines in rats with 6-hydroxydopamine lesions of caudate or nucleus accumbens.

The behavioral actions of some novel aporphines have been examined in rats with selective unilateral 6-hydroxydopamine (6OHDA)-induced destruction of nigrostriatal dopaminergic neurons, and in rats with bilateral 6OHDA-induced destruction of mesolimbic dopaminergic neurons. Dopaminomimetics such as apomorphine (APO) in these animal models elicit circling behavior and locomotor activity respectively. In animals with unilateral nigrostriatal lesions (-)-2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA) and (-)-10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) elicited weak, but prolonged, contraversive circling, whereas (-)-2,10,11-trihydroxyaporphine (2-OH.APO) was inactive. In animals with bilateral destruction of mesolimbic dopaminergic neurons TNPA and MDO-NPA elicited a strong stimulation of locomotor activity, while 2-OH.APO was inactive. The results suggest that TNPA and MDO-NPA, but not 2-OH.APO, exert central dopaminomimetic effects in vivo. The results are also consistent with previous data indicating that N-propyl substitution of aporphines causes a relative enhancement of activity in animal models which emphasise effects at mesolimbic rather than striatal dopaminergic receptors.