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

Abstract

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.

Different effects of chronic THC on the neuroadaptive response of dopamine D2/3 receptor‐mediated signaling in roman high‐ and roman low‐avoidance rats

“…In addition, acute THC was less effective in RLA than in RHA rats at inhibiting locomotor activity. Given the implication of striatal CB 1 R in the control of motor behaviors (Moghaddam, Khodayar, Abarghouei, & Ardestani, ; Sanudo‐Pena, Force, Tsou, Miller, & Walker, ), the lower locomotor depressant effect of acute THC together with the lower CB 1 R mRNA levels in striatum suggests a lower CB 1 R‐mediated signaling in RLAs as compared to RHAs. Contrasting with this blunted effect of acute THC in RLAs, chronic THC led to an increased density and functional sensitivity of D 2/3 R signaling in RLA but not in RHA rats.…”

Activation of cannabinoid type 1 receptors decreases the synchronization of local field potential oscillations in the hippocampus and entorhinal cortex and prolongs the interresponse time during a differential‐reinforcement‐of‐low‐rate task

“…The effective dosage for ACPA in the hippocampal formation is inconclusive. In the striatum, 100 ng of ACPA improves movement activity in a Parkinson's rat model (Moghaddam, Khodayar, Abarghouei, & Ardestani, 2010). Moreover, 0.125–5 ng of ACPA in the amygdala (Zarrindast et al., 2008) and 5–7.5 ng of ACPA in the ventral hippocampus (Mohammadmirzaei, Rezayof, & Ghasemzadeh, 2016) result in some cognitive effects.…”

The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases

“…AM251 alleviated the catalepsy in a dose dependent manner. In contrast, the administration of ACPA increased the catalepsy [ 208 ]. Such studies prove that rCB1 antagonist could be the next step as drug of choice in the alleviation of motor symptoms in PD.…”