S-adenosyl-L-methionine decreases motor activity in the rat: similarity to Parkinson's disease-like symptoms.
S-Adenosyl-L-methionine has been shown to cause Parkinson's disease-like effects that include hypokinesia, tremor, rigidity, and abnormal posture. S-Adenosyl-L-methionine is the rate-limiting endogenous methyl donor. Its biochemical role, which includes the metabolism of dopamine and the synthesis of acetylcholine, also resembles the changes that occur in Parkinson's disease. Therefore, S-adenosyl-L-methionine may play a role in Parkinson's disease-like motor impairments. In this study we manipulated the levels of S-adenosyl-L-methionine in the brain of rats and quantified the changes in hypokinetic type motor activity that seems to occur also in Parkinsonism. Male Sprague-Dawley rats were anesthetized with chloral hydrate (400 mg/kg/rat), cannulated, injected into the lateral ventricle with S-adenosyl-L-methionine or saline, and their motor activity was measured in a Digiscan Animal Activity Monitor. Other behaviors were also observed. S-Adenosyl-L-methionine caused hypokinesia, tremor, rigidity, and abnormal posture in rats. Motor activity was significantly decreased within 2 min postinjection. The hypokinesia was maximal at 60 min, at which time a 65, 75, and 90% decrease for total distance, number of movements, and the ratio of total distance to the number of movements occurred, respectively. The hypokinetic effect of S-adenosyl-L-methionine was dose dependent. A 65.0 and 51.3% decrease in total distance and number of movements, respectively, were observed following 9.38 x 10(-9) mol. The 5.0 x 10(-8) mol caused a reduction of 73.42 and 57.66% and 4.0 x 10(-7) mol/rat caused a 94.9 and 78.43% decrease, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Crowell
B G
BG
Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37221.
Benson
R
R
Shockley
D
D
Charlton
C G
CG
D000818:Animals; D001522:Behavior, Animal; D002395:Catecholamines / Q000378:metabolism; D007103:Immobilization; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009069:Movement Disorders; D010300:Parkinson Disease; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000009:adverse effects* / Q000378:metabolism; D014202:Tremor / Q000139:chemically induced
D002395:Catecholamines; D007980:Levodopa; D012436:S-Adenosylmethionine