CONDITIONED APOMORPHINE-INDUCED TURNING IN 6-OHDA-LESIONED RATS

Apomorphine-induced turning has been used to evaluate the extent of un ilateral nigrostriatal denervation after 6-hydroxydopamine (6-OHDA) le sions and subsequent functional striatal reinnervation by catecholamin ergic grafts. It has been noted that the pregraft rotational pattern i s usually double peaked and that fetal ventral mesencephalic grafts or dopaminergic drugs will alter the second peak but leave the first rel atively unchanged. We hypothesized that the first peak may be the resu lt of factors extrinsic to the nigrostriatal dopamine system, specific ally a conditioned turning response, and would, therefore, be unpertur bed by the above treatments which increase dopaminergic (DA) inputs. T his was investigated by injecting 6-OHDA, unilaterally, into the nigro striatal pathway of several groups of young Fisher 344 rats. One exper imental group was repeatedly tested with 0.05 mg/kg apomorphine and th e rotations quantified. A second group received similar injections of apomorphine but were prevented from rotating. Vehicle control animals were also studied for both of the above experimental groups. Subsequen t to the above treatment, all animals were tested unrestrained repeate dly on apomorphine. Our results support the conditioned response hypot hesis in that the first peak is not present with the initial unrestrai ned apomorphine behavioral trial but is present upon the second and su bsequent unrestrained trials. Moreover, the restrained but apomorphine -injected rats, as well as the control animals, manifest no first peak upon their first freely moving apomorphine test; the second and subse quent unrestrained apomorphine trials, in these groups, do manifest a first peak. We conclude that the first peak represents respondently (P avlovian) conditioned rotations and is, therefore, an indirect seconda ry behavioral result of unilateral nigrostriatal dopaminergic denervat ion and repeated apomorphine administration in an environment allowing unimpeded movements. These rotations are unlikely to be directly rela ted to the cellular changes induced by dopaminergic manipulations in t his system and, therefore, their presence in studies of striatal dener vation and reinnervation using apomorphine-induced turning behavior sh ould be interpreted accordingly.