crotononitrile and Movement-Disorders

A single oral administration of allylnitrile, crotononitrile or 2-pentenenitrile in rats induced behavioral abnormalities, such as head-twitching, head weaving, hindlimb abduction, backward pedaling and pivoting. The head-twitching, which was most consistently observed, was suppressed by serotonin (5-HT) antagonists, cyproheptadine or methysergide or by the 5-HT depleter, dl-p-chlorophenylalanine but was accentuated by the 5-HT releaser, dl-p-chloroamphetamine. The results suggest that the 5-HT system is involved in producing the behavioral abnormalities. To discover the effects of allylnitrile, crotononitrile and 2-pentenenitrile on the metabolism of 5-HT and dopamine, 6 areas of the brain of the rat were examined on days 1, 6, 15 and 30 after injection. Each of the nitriles caused significant increases in the level of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and in the ratio of 5-HIAA/5-HT, one day after injection. The increase in 5-HIAA was most remarkable, suggesting an enhancement of the serotonergic system. The three nitriles had no effect on the metabolism of dopamine, over a period of 30 days.

Topics: Animals; Behavior, Animal; Brain; Cyproheptadine; Fenclonine; Hydroxyindoleacetic Acid; Male; Methysergide; Movement Disorders; Nitriles; p-Chloroamphetamine; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin

A single oral dose of allylnitrile (ALN) in mice pretreated with CCl4 induced behavioral abnormalities such as circling, hyperactivity, and head twitching, which lasted for a 4-month observation period. Histopathologically hemorrhage, demyelinated fibers and necrotic neurons were observed in the midbrain and pons 40 to 50 days after the administration of ALN. The head twitching was either reduced by treatment with serotonin and dopamine antagonists or enhanced by a serotonin releaser, suggesting that both serotonin and dopamine systems are involved in the behavioral abnormalities by ALN. These disorders by ALN may be used as an animal model of the dyskinetic syndrome.

Topics: Animals; Behavior, Animal; Brain; Carbon Tetrachloride; Cerebral Hemorrhage; Male; Mice; Movement Disorders; Nitriles; Time Factors