Hemopressin increases penicillin-induced epileptiform activity in rats

Abstract

OBJECTIVE: 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. METHODS: 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 mu l/i.c.v/saline), hemopressin groups (Group II: 0.025 mu g/i.c.v; Group III: 0.075 mu g/i.c.v; Group IV: 0.15 mu g/i.c.v; Group V: 0.3 mu g/i.c.v; Group VI: 0.6 mu g/i.c.v; Group VII: 1.2 mu g/i.c.v; Group VIII: 2.4 mu g/i.c.v). The various doses of hemopressin were injected intracerebroventricularly (i.c.v) 30 minutes after penicillin (2.5 mu 1) injection. After hemopressin injection, ECoGs were recorded for three hours. RESULTS: Hp at doses of 0.075, 0.15, 0.3, 0.6, 1.2 and 2.4 mu g/kg significantly increased the frequency of epileptiform ECoG activity compared to penicillin-injected group without changing the amplitude. The 0.6 mu g hemopressin was the most effective dose to increase the epileptiform activity (p < 0.05) while the dose of 0.025 mu g hemopressin was non-effective (p > 0.05). CONCLUSIONS: The results of this study provided electrophysiological evidence for hemopressin to be modulating penicillin-induced epileptiform activity by acting as CBI receptor antagonist. Further studies are required to elucidate the involved mechanism underlying this effect (Fig. 3, Ref. 40).