Postponement of symptoms of hereditary muscular dystrophy in chickens by 5-hydroxytryptamine antagonists

Abstract

THE commoner forms of muscular dystrophy, both in man and in animals, are determined by a single gene change, but the mechanism whereby the complex set of symptoms develops is unknown. Chickens homozygous for muscular dystrophy have been bred, and form probably the closest animal model for the human disease so far investigated^1,2. Dystrophic line 304 of the Davis (California) flock, for example, has been bred for rapid appearance of the symptoms and shows some signs of muscle weakness at 7–10 d ex ovo, whereas a normal line (200) of chickens with closely related genetic background is also available^1,2. Two of us have reviewed³ evidence that 5-hydroxytryptamine (5-HT) is involved in some way in the development of the symptoms of muscular dystrophy, and reported that administration of a 5-HT antagonist, methysergide, retards the development of the symptoms in line 304 chickens. We report here that this effect is more general, in that a second anti-serotoninergic drug of entirely different chemical structure, cyproheptadine, is also effective, and that a combination of the two agents is beneficial.