Hemopressin increases penicillin-induced epileptiform activity in rats

Hemopressin (Hp) is the first peptide ligand described for the CB1 cannabinoid receptor. Therefore, we aimed to investigate the effect of hemopressin on pencillin-induced epileptiform activity by using electrophysiological recording (ECoG) technique.

Male Wistar rats were anesthetized with urethane (1.25 g/kg), and epileptiform activity was induced by intracortical injection of penicillin (500 IU). Animals were randomly divided into eight groups. Subsequently, the rats were administered with saline or hemopressin as follows: saline control group (Group I: 2 μl/i.c.v/saline), hemopressin groups (Group II: 0.025 μg/i.c.v; Group III: 0.075 μg/i.c.v; Group IV: 0.15 μg/i.c.v; Group V: 0.3 μg/i.c.v; Group VI: 0.6 μg/i.c.v; Group VII: 1.2 μg/i.c.v; Group VIII: 2.4 μg/i.c.v). The various doses of hemopressin were injected intracerebroventricularly (i.c.v) 30 minutes after penicillin (2.5μl) injection. After hemopressin injection, ECoGs were recorded for three hours.

Hp at doses of 0.075, 0.15, 0.3, 0.6, 1.2 and 2.4 μg/kg significantly increased the frequency of epileptiform ECoG activity compared to penicillin-injected group without changing the amplitude. The 0.6 µg hemopressin was the most effective dose to increase the epileptiform activity (p 0.05).

The results of this study provided electrophysiological evidence for hemopressin to be modulating penicillin-induced epileptiform activity by acting as CB1 receptor antagonist. Further studies are required to elucidate the involved mechanism underlying this effect (Fig. 3, Ref. 40).