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Objectives This study investigated the involvement of different types of K+ channels and PPARγ receptors in the antidepressant-like effect of diphenyl diselenide in mice. Methods Mice were pretreated with subeffective doses of K+ channel inhibitors (tetraethylammonium, glibenclamide, charybdotoxin and apamin), openers (cromakalim, minoxidil), GW 9662 (a PPARγ antagonist) or vehicle. Thirty minutes later the mice received diphenyl diselenide in either an effective or a subeffective dose, 30 min before a tail-suspension test. Key findings Pre-treatment with tetraethylammonium, charybdotoxin or apamin combined with a subeffective dose of diphenyl diselenide was effective in decreasing the immobility time in the mouse tail-suspension test. The reduction in the immobility time elicited by an effective dose of diphenyl diselenide in this test was prevented by the pretreatment of mice with minoxidil and GW 9662. Conclusions Diphenyl diselenide elicited an antidepressant-like effect and this action was mediated, at least in part, by modulation of K+ channels and PPARγ receptors.

Objectives The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)-2,3-bis(4-chlorophenylselanyl)prop-2-en-1-ol]. Methods The effects of oral bis selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12-myristate 13-acetate (PMA), 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) and pros-taglandin E2. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide. Key findings Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66–39.45) and 15.86 (12.17–20.67) mg/kg and maximal inhibition of 65 ± 3% and 90 ± 1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31 ± 2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide caused a significant inhibition (42 ± 5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64 ± 3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE2, PMA and 8-BrcAMP. The antinociceptive effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5-HT2a receptor antagonist), ondansetron (a 5-HT3 receptor antagonist) and ranitidine (a histamine H2-receptor antagonist). Conclusions Glutamatergic, prostaglandin E2, serotonergic (5-HT2a and 5-HT3) and histamine H2 receptors are involved in the antinociceptive effects of bis selenide in mice. The interaction of bis selenide with protein kinase C and A signalling pathways was also demonstrated.

This study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe)2) in the formalin test. Mice were pre-treated with (PhSe)2 by the oral route (0.1–100 mg kg−1), 30 min before formalin injection. To address some of the mechanisms by which (PhSe)2 inhibits formalin-induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe)2 was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe)2 (10 mg kg−1, p.o.) was prevented by intrathecal injection of K+ channel blockers such as apamin and charybdotoxin (small- and large-conductance Ca2+-activated K+ channel inhibitors, respectively) and tetraethylammonium (TEA, a non-selective voltage-dependent K+ channel inhibitor), but not glib-enclamide (an ATP-sensitive K+ channel inhibitor). The antinociceptive action caused by (PhSe)2 (10 mg kg−1, p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (Nω-nitro-l-arginine, L-NOARG) and the soluble guanylate cyclase inhibitors 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca2+ and K+ channel pathways in the antinociceptive effect caused by (PhSe)2.