Background and objective: Developing
therapy for non-motor symptoms of
Parkinson's disease (PD) is important for improving patients' quality of life. Previously, we reported that the
ghrelin receptor agonist,
HM01 normalized the decreased 4-h fecal output and
levodopa-inhibited gastric emptying in
6-OHDA rats, and activated selective areas in brain and spinal cord. In this study, we evaluated whether chronic
HM01 treatment influences motor functions and/or has beneficial effects on non-motor symptoms including alterations of
body weight and composition, defecation, feeding and water intake in
6-OHDA rats. Methods: Male rats were microinjected unilaterally into the medial forebrain bundle with either vehicle or
6-OHDA. Three weeks later, we assessed basal body weight, and 24-h fecal output (pellets, weight, dry weight and water content), water intake and food intake (ingested and spillage). Then,
HM01 (3 mg/kg) or vehicle was given per gavage daily for 10-12 days and the same parameters were re-assessed daily. Motor behavior (stepping and rotations tests), body composition were monitored before and after the
HM01 treatment. Results:
6-OHDA rats showed motor deficits in rotation test induced by
apomorphine and stepping test. They also displayed a significant reduction in
body weight, water consumption, fecal weight and water content and an increase in food spillage compared to vehicle microinjected rats. Daily oral treatment of
HM01 did not modify motor alterations compared to vehicle but significantly increased the
body weight, fat mass, and 24-h fecal weight, fecal water content, food and water intake in
6-OHDA rats, while
HM01 had no significant effect in vehicle microinjected rats. Fecal weight and water content were both correlated with water intake, but not with food intake. Fat mass, but not
body weight, was correlated with food intake.
HM01 effects were significant after 24 h and remained similar during the treatment. Conclusions: Chronic treatment with
ghrelin agonist, HM01 improved several non-motor symptoms in the rat PD model induced by
6-OHDA lesion including the decrease in
body weight, water consumption, fecal weight and water content, and increased food intake while not improving the motor deficits. These findings provide pre-clinical evidence of potential benefits of
ghrelin agonists to alleviate non-motor symptoms in PD patients.