Effect of Testosterone on Haloperidol Induced Catalepsy in Male Rats

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease involving nigrostriatum neurons. Recent studies have indicated a higher prevalence of PD in male gender. On the other hand testosterone deficiency is more common among male parkinsonian patients in compare to healthy men. Objective: This study was aimed to investigate the effect of testosterone hormone on a parkinsonian motor symptom, catalepsy, in male rats. Catalepsy is inability to correct externally imposed postures, and the muscle stiffness comes towards this failure. Methods: The study carried out on male Wistar rats weighing 220-230g. In order to induce catalepsy in animals, haloperidol (1 mg/kg, i.p) as D2 antagonist was administered before testing animals via standard bar test. Animals were gonadectomized to investigate testosterone elimination effect on catalepsy, and also the androgen receptor blocker, flutamide (10, 20, 30 mg/kg i.p) , and the aromatase inhibitor, letrozole (4 mg/kg s.c), were administered in certain groups of animals. The standard bar test method was used to evaluate induced catalepsy. Results: Haloperidol 1 mg/kg, i.p, was able to induce ambient catalepsy (p< 0.0001). Results of standard bar test represented that gonadectomy worsened the catalepsy symptom (p< 0.05) and subchronic testosterone replacement could return this effect (p< 0.001). While low dose flutamide administration represented an improvement in cataleptic symptoms, higher doses were more cataleptic. Letrozole administration represented nearly the same cataleptic symptoms as the control group of animals. Conclusion: Testosterone deficiency increases catalepsy and testosterone (1 mg/kg, i.p) subchronic replacement can significantly be effective in remission. It seems that the effect of testosterone on improvement of cataleptic symptoms is through its influence on androgenic receptors.