The electrophysiological and behavioral evaluation of the peptide hemopressin and cannabinoid CB1 receptor agonist and antagonist in pentylenetetrazol model of epilepsy in rats

Abstract

This study endeavoured to assess the effect of hemopressin (Hp), a nano peptide obtained from the alpha chain of hemoglobin, on chronic epileptic activity and its potential correlation with cannabinoid receptor type 1 (CB1). Male Wistar albino rats (230-260 g) were used. The kindling process was conducted by administering a sub-convulsant dose of pentylenetetrazol (PTZ) (35 mg/kg, i.p) three times a week for a maximum of 10 weeks. Tripolar electrodes and external cannula guides for intracerebroventricular (i.c.v) injections were surgically implanted in the skulls of kindled rats. On the day of the experiment, doses of Hp, AM-251, and ACEA were administered prior to the PTZ injections. Electroencephalography recordings and behavioural observations were conducted simultaneously for 30 min after the PTZ injection. The administration of Hp (0.6 μg, i.c.v) resulted in a decrease in epileptic activity. The CB1 receptor agonist ACEA (7.5 μg, i.c.v) showed an anticonvulsant effect, but the CB1 receptor antagonist AM-251 (0.5 μg, i.c.v) displayed a proconvulsant effect. The co-administration of Hp (0.6 μg, i.c.v) and ACEA (7.5 μg, i.c.v) and of Hp (0.6 μg, i.c.v) and AM-251 (0.5 μg, i.c.v) produced an anticonvulsant effect. However, when AM-251 was administered prior to Hp, it produced a proconvulsant impact that overrode Hp's intended anticonvulsant effect. Interestingly, the co-administration of Hp (0.03 μg) + AM-251 (0.125 μg) unexpectedly exhibited an anticonvulsant effect. Electrophysiological and behavioural evaluations demonstrated the anticonvulsant effect of Hp in the present model, highlighting the possibility that Hp may act as an agonist for the CB1 receptor.

Keywords: ACEA; AM-251; Cannabinoid receptor; Epilepsy; Hemopressin; PTZ.