Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock in mice

Abstract

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H 1 -receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

Intracerebroventricular Effects of Histaminergic Agents on Morphine‐Induced Anxiolysis in the Elevated Plus‐Maze in Rats

“…We evaluated a probable interaction between histaminergic agents and morphine‐induced anxiolysis in the elevated plus‐maze test of anxiety. Some reports have shown an interaction between opioid and histaminergic systems in water intake (Eidi et al 2003), memory (Zarrindast et al 2002) and also in convulsions (Karadag et al 2000) in animal experiments. Moreover, human drug addicts are known to use the combination of the opioid pentazocin and the H 1 receptor antagonist, tripelenamine as a substitute for heroin (Lang & Jasinski 1984).…”

“…Histamine as a central neurotransmitter (Onodera et al 1994) is concentrated in the tuberomamillary nucleus of the posterior hypothalamus with efferent varicose fibers to almost all parts of the brain (Watanabe et al 1984). There is agreement that histamine and histaminergic system in the brain have an important role in several physiological processes such as cognition and novel environment‐motivated exploration (Zimmermann et al 1999; Ikarashi & Yuzurihara 2002). Some studies have documented the involvement of the histaminergic system in modulation of anxiety‐like behaviours in animals (Privou et al 1998; Malmberg‐Aiello et al 2002).…”

Involvement of Mast Cells in Adenosine-Mediated Bronchoconstriction and Inflammation in an Allergic Mouse Model

“…Chronic treatment with C48/80 has been shown to deplete mast cells of their granular contents (Jaffery et al, 1994;Karadag et al, 2000). Adenosine is involved in asthma through its ability to promote or enhance mediator release from mast cells (Peachell et al, 1988;Jacobson and Bai, 1997).…”

“…BALB/c mice were injected chronically to deplete mast cells of their granular contents. This protocol is modified from previous work by Karadag et al (2000). C48/80 was injected i.p.…”