Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity of parkinsonian rats induced by reserpine.

It has been observed cannabinoid CB1 receptor signalling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson's disease (PD) patients. These evidences suggest that the blocking of cannabinoid CB1 receptors might be beneficial to improve movement disorders as a sign of PD. In this study, a dose-response study of the effects of intrastriatal injection of a cannabinoid CB1 receptor antagonist, AM251 and agonist, ACPA, on movement activity was performed by measuring the catalepsy of reserpinized and non-PD (normal) rats with bar test. Also the effect of co-administration the most effective dose of AM251 and several doses of ACPA were assessed. AM251 decreases the reserpine induced catalepsy in dose dependent manner and ACPA causes catalepsy in normal rats in dose dependant manner as well. AM251 significantly reverse the cataleptic effect in all three groups (1, 10, 100 ng/rat) that received ACPA. These results support this theory that cannabinoid CB1 receptor antagonists might be useful to alleviate movement disorder in PD. Also continuance of ACPA induced catalepsy in rats after AM251 injection can indicate that other neurotransmitters or receptors interfere in ACPA induced catalepsy. Based on the present finding there is an incomplete overlapping between cannabinoid CB1 receptor agonist and antagonist effects.