Pregnancy decreases the threshold for cocaine-induced convulsions in the rat.
The objective of this study was to test our hypothesis that pregnancy modifies the central nervous and cardiovascular toxicity of cocaine. Ten chronically catheterized term pregnant rats and 13 chronically catheterized nonpregnant female rats were infused with cocaine (2 mg/kg/min) intravenously to observe the sequential toxic manifestation of cocaine from mild central nervous stimulation (hyper-locomotor activities) to fatal cardiovascular collapse. Arterial blood samples were withdrawn at the onset of major toxic signs or symptoms--namely convulsion, hypotension, and circulatory collapse--for determination of cocaine concentrations and plasma cholinesterase activity. The dosage and plasma concentrations of cocaine associated with the onset of convulsions and cardiovascular depression were significantly lower in pregnant rats when compared with the nonpregnant animals. The mean time required to develop convulsions in the pregnant rat was significantly shorter (21 minutes) than that in the nonpregnant animal (33 minutes). However, once convulsive activity had developed, the time interval to achieve circulatory collapse was similar in both groups. Although the baseline plasma cholinesterase activity was higher in the pregnant rats than in the nonpregnant ones, the values in the samples obtained from the pregnant group at the onset of circulatory collapse were similar to the baseline values for the nonpregnant group. These findings suggest that a higher enzyme activity does not protect the development of toxic manifestations in the pregnant rat as compared to the nonpregnant animal when cocaine was administered at the same infusion rate.
Morishima
H O
HO
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY.
Masaoka
T
T
Hara
T
T
Tsuji
A
A
Cooper
T B
TB
D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology; D002802:Cholinesterases / Q000097:blood; D003042:Cocaine / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006339:Heart Rate; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced*; D013997:Time Factors
D002802:Cholinesterases; D003042:Cocaine