ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). The events, which trigger and/or mediate the loss of nigral DA neurons, however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs for Parkinsonism. Administration of haloperidol (1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50 and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced catalepsy. The results indicate that BR-16A or ashwagandha has protective effect against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A could be used in preventing the drug-induced extrapyramidal side effects and may offer a new therapeutic approach to the treatment of Parkinson's disease.
Subject(s)
Animals , Catalepsy/chemically induced , Female , Haloperidol/toxicity , Male , Medicine, Ayurvedic , Mice , Parkinsonian Disorders/chemically induced , Phytotherapy , Plant Extracts/therapeutic use , Plants, Medicinal , Reserpine/toxicity , WithaniaABSTRACT
Reserpine-induced catalepsy is a widely accepted animal model of Parkinson's disease. In the present study reserpine (2.5 mg/kg, ip) 20 hr and alpha-mehyl-para-tyrosine (AMPT; 200 mg/kg, ip), one hour before the experiment induced significant catalepsy in rats as assessed by bar test. There was a significant increase in the time spent on the bar in bar test as compared to the control untreated rats. L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination, a conventional therapy was less effective in reversing reserpine-induced catalepsy. Pretreatment with FK506, a neuroprotectant (0.5-2 mg/kg, po) not only dose dependently reduced the catalepsy in reserpine-treated rats but a lower dose (1 mg/kg) potentiated the motor stimulant actions of sub threshold dose of L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination. Anticataleptic effect of FK506 was blocked dose dependently by specific D2 receptor blocker sulpiride (25-100 mg/kg, ip). In conclusion, the findings of the present study suggest that FK506 has an indirect modulatory action on the dopamine D2 receptors. FK506 being a neuroprotectant, could be used as an effective adjunct to L-dopa for the treatment of neuroleptic-induced extrapyramidal side effects.
Subject(s)
Animals , Antiparkinson Agents/therapeutic use , Catalepsy/chemically induced , Drug Therapy, Combination , Female , Immunosuppressive Agents/therapeutic use , Levodopa/therapeutic use , Male , Rats , Rats, Wistar , Reserpine/toxicity , Tacrolimus/therapeutic useABSTRACT
This study was conducted on 40 male rats divided into four equal groups: Two test groups receiving reserpine 0.1 mg/kg subcutaneously for 30 and 60 consecutive days and the other two received distilled water subcutaneously for the same period and served as controls. Sex organs weights, semen analysis, level of testosterone as well as histopathological examination were the criteria used to evaluate the reproductive performance of treated male rats. Reserpine significantly decreased testicular weight, sperm cells concentration, live sperms, percentage of sperm motility, velocity and plasma testosterone level. A significant increase in the percentage of sperm abnormalities was observed in treated groups. Histopathologically, reserpine induced mild to severe degenerative changes in the testes
Subject(s)
Animals, Laboratory , Male , Testosterone/blood , Testis/pathology , Sperm Count , Semen/analysis , Reserpine/toxicity , Rats , Sperm Motility , Sperm CountABSTRACT
Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.