Neurochemical evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine.
Clonidine (CLON), an alpha-2 adrenergic agonist, is widely used to reduce hypertension; it is also recommended for blocking acute opiate withdrawal. Lofexidine (LOF), a CLON analog, is an investigational compound being readied for the marketplace. Since exposure to both drugs is likely to occur in the last two trimesters of human pregnancy, it is important to determine whether such exposure can have effects upon brain or behavior of offspring. Pregnant CD rat dams were given daily subcutaneous injections of saline, CLON, or LOF on days 8 through 20 of gestation. Maternal weight during gestation, neonatal weight and neurochemical measures were monitored. Maternal body weight was reduced in a dose dependent manner. At PND 1 brain ornithine decarboxylase (ODC) activity was reduced in LOF- but not CLON-exposed pups of both sexes. At this age no alteration was seen in whole brain catecholamine levels or in whole brain alpha-2-adrenergic binding.
Ali
S F
SF
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Holson
R R
RR
Pizzi
W J
WJ
Newport
G D
GD
Slikker
W
W
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008565:Membrane Proteins / Q000032:analysis; D018377:Neurotransmitter Agents / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; C016986:apraclonidine; D009955:Ornithine Decarboxylase; D003000:Clonidine; C025655:lofexidine