Resumo

Objectives Animal models are being used to study alterations caused by the Parkinson Disease (PD). However, in general, pharmacological models do not express the progressive nature of the disease, causing immediate severe motor impairment with one administration. Reserpine administration in rodents has been suggested as a pharmacological model of PD based on the effects of this monoamine-depleting agent on motor activity. Recently, we observed that a single administration of reserpine induces cognitive deficits with lower doses than those usually given to induce motor impairment (Prog. Neur. Psy. Biol. Psych. 32: 1479, 2008). In this study, we evaluate possible cognitive and motor progressive effects of repeated administration of low doses of reserpine. Methods and Results Male Wistar rats (5-6 months old), received 15 s.c. injections of vehicle (VEH) (n=8) or 0.1 mg/kg reserpine (RES) (n=8) every other day. Throughout the treatment (before the beginning, 24 and 48 h after each injection and 72h after the last injection) the rats were evaluated for duration of cataleptic behavior (s), which was significantly increased in the RES group from 48 h after the 8th injection to 72 h after 10th injection (mean  S.E.M were 5.8±1.2 (VEH), 36±12.9 (RES) and 4.6±1.2 (VEH), 71.5±15.5 (RES), respectively). Orofacial movements were also assessed before the beginning of the treatment, 24 h after the 5th injection and 24 h and 48 h after the 10th injection. Significant increases in the number of vacuous chewing movements and in the number of tongue protrusions were found in the RES group 24 h and 48h after the 10th injection (Vacuos chewing: 69±11.9 (VEH) and 132±14.4 (RES), 62.5±11.7 (VEH) and 112.8±12.7 (RES), respectively). Tongue protrusions: 6.8±2.5 (VEH) and 19±3.2 (RES); 3.1±1.07 (VEH) and 12.1±2.8 (RES), respectively. Motor activity was also evaluated by distance traveled in an open field (m) after the 4th and 8th injections and significant decrement induced by reserpine was found only after the 8th injection (VEH: 15.2±2.5, RES: 5.5±0.6). Possible cognitive effects were evaluated by the discriminative avoidance task, accomplished after the 7th injection. Aversive arm exploration in the test session (% of time spent) by the RES group was increased but did not reach statistical significance (VEH: 14.6±9.9, RES: 24.1±10.7). A novel object recognition task was accomplished after the 8th injection, in which both groups presented increased exploration (s) of new object compared to old object in the test session (VEH: 41.6±8.5 and 23.1±6.6; RES: 39.5±10.7 and 4.5±2.02; respectively). Conclusions Repeated treatment with low alternated doses of reserpine progressively induced alterations in motor function, indicating a possible application of this model in the study of the progressive nature of PD. However, cognitive deficits were not clearly demonstrated (as we had verified in a previous study), maybe due to the great variability of rats’ behavior in the discriminative avoidance paradigm. More studies are needed to verify if the progressive development of symptoms induced by this scheme of reserpine treatment can be found for cognitive symptoms as well.