Non-dopaminergic mechanisms in the turning behavior evoked by intranigral opiates

The turning effects of the unilateral intranigral injection of morphine and of different analogs of dynorphin and enkephalin were studied. All injections were made in awake rats through cronically implanted guide cannulae. Dynorphin1-13 at a dose of 10 micrograms (0.6 nmol) and dynorphin1-17 at a dose of 2 micrograms (0.9 nmol) produced contralateral circling when injected unilaterally in the substantia nigra (SN), lasting for about 1 h. D-Ala-dynorphin1-17, a more stable analog of dynorphin, produced at a dose of 2 micrograms (0.9 nmol), a longer-lasting effect. Injections of different enkephalin analogs were also made into the SN, [D-Ser2]-Leu-enkephalin (10 micrograms, 14.5 nmol) and [D-Ala2,D-Ala3]-Met-enkephalin (10 micrograms, 15 nmol) also produced contralateral circling after unilateral intranigral injection. This behavior lasted for 60-90 min, depending on the different enkephalins used. As already reported by Iwamoto and Way18 morphine also produced contralateral circling when injected into the SN. The circling evoked by all these opiates was completely antagonized by 5 mg/kg of naltrexone s.c. In order to study the role of the dopaminergic nigrostriatal system, we made unilateral lesions of the medial forebrain bundle (MFB) with 6-hydroxydopamine (6-OHDA) and kainic acid lesions of the striatum and we looked at the effect elicited by these lesions on the behavior produced by the above compounds when injected into the SN. The lesion of the dopaminergic nigrostriatal system failed to affect either the number of turns or the duration of the contralateral circling produced by unilateral injections of morphine, dynorphin and enkephalin analogs into the SN correspondent to the lesioned side. On the other hand kainate lesions of the body of the caudate potentiated the turning induced by intra-SN morphine and dynorphin. Therefore it appears that the dopaminergic nigrostriatal system is not essential in the expression of the contraversive turning behavior produced by intranigral injections of endogenous opiates or morphine and that opiates might produce dopamine-like effects indirectly, through the inhibition of nigral non-dopaminergic output neurons.