Neuroprotective Effects of Low Dose Anandamide in Pentylenetetrazole-Induced Kindling in Rats

Omar M. E. Abdel-Salam¹, Amany A. Sleem², Marawan Abd El-Baset Mohamed Sayed², Eman R. Youness³and Nermeen Shaffie⁴

¹Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt.

²Department of Pharmacology, National Research Centre, Cairo, Egypt.

³Department of Medical Biochemistry, National Research Centre, Cairo, Egypt.

⁴Department of Pathology, National Research Centre, Cairo, Egypt.

Corresponding Author E-mail: omasalam@hotmail.com

Abstract: Anandamide (N-arachidonoylethanolamine) is an endogenous cannabinoid receptor CB1 ligand that exhibits neuroprotective effects in the brain. In this study, the effect of exogenously given anandamide on pentylenetetrazole (PTZ)-induced chemical kindling oxidative stress and brain damage in rats was studied. Rats were intraperitoneally (i.p.) injected with 35 μg/kg PTZ once every 48 hours for 12 times to induce seizures. Anandamide was i.p. given. 30 min prior to PTZ injection at 100 or 200 μg/kg. Injections of PTZ induced significant increase in brain lipid peroxidation (malondialdehyde: MDA), and nitric oxide associated with marked decrease in brain reduced glutathione (GSH). There were also significant decrements in acetylcholinesterase (AChE) concentration, butyrylcholinesterase (BChE) and paraoxonase-1 (PON-1) activities in brain tissue of PTZ injected rats. Meanwhile, there was no significant effect for PTZ on the concentration of brain neutrophil elastase. Anandamide administered at 100 and 200 μg/kg significantly decreased MDA and increased GSH contents and at 200 μg/kg significantly decreased nitric oxide in brain of PTZ-treated rats. The drug also caused significant increments in AChE concentration and PON-1 activity but had no significant effect on BChE or neutrophil elastase in rats treated with PTZ. Anandamide given at the dose of 200 μg/kg significantly decreased the mean seizure scores over the study period by 22.3% and the frequency of myoclonic jerks and rearing (stage 3) by 56.7% compared with the vehicle-treated group. Anandamide given at 100 and 200 μg/kg completely inhibited the development of generalized tonic-clonic seizures (stage 5). It is concluded that in the PTZ-induced seizures, the cannabinoid receptor CB1 agonist anandamide decreases brain oxidative stress, neuronal injury, and exerts an antiepileptic activity.

Keywords: Anandamide; Endocannabinoids; Kindling; Neurodegeneration; Oxidative Stress; Pentylenetetrazole

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