Effects of bilateral striatal 6-OHDA lesions on circadian rhythms in the rat: a radiotelemetric study.

The present work aims to document, in a previously described animal model of Parkinson (double bilateral striatal injection of 6-OHDA), the possible modifications of circadian markers rhythms i.e. temperature (T), heart rate (H) and locomotor activity (A) registered continuously by telemetry, in order to evaluate a possible perturbation of the circadian rythmicity. H, T and A were measured by radiotelemetry after surgical implantation of the transmitters (Data Sciences). After a recovery period, the study was divided into a control period (C) for baseline measurements of T, H and A daily rhythms. Then, the stereotaxic 6-OHDA striatal lesion was done to a group of 4 rats while the control rats were injected into striata with saline; a second period of four registration weeks was observed [D 1-7 (W1), D 8-14 (W2), D 15-21 (W3), D 22-28 (W4)]. Finally, at the end of this period the seven rats were decapited in order to determine their striatal dopamine (DA) content. Our data document that the circadian rhythms of H, T and A were differently affected according to time. Thus, a temporary loss of circadian periodicity was observed particularly for heart rate. 6-OHDA-induced modifications of H, T and A circadian rhythm characteristics were also observed: a significant decrease of the mesor was observed for the three rhythms as well as a phase advance. Concerning the amplitude of these rhythms, only H was significantly decreased. These perturbations were observed during the four weeks following the intervention, never reaching the initial control levels. Such observed perturbations would supply a basis for the future study of the chronopharmacology of antiparkinsonian drugs.