Behavioral evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine.
Clonidine (CLON), is a widely used antihypertensive agent with a potential for expanded therapeutic application in combating drug withdrawal symptoms in opiate and alcohol addiction. Recently, CLON and an analogue lofexidine (LOF) have been shown to block the opiate withdrawal syndrome in a variety of species, including man. One new application of these agents may be as an alternative to methadone maintenance for pregnant opiate addicts. Any consideration along these lines will require screening for reproductive outcome and behavioral teratogenic effects. Dams were given s.c. injections of CLON (0.16 or 0.64 mg/kg) of LOF (0.64 or 2.56 mg/kg) once daily from gestational day (GD) 8-20. Neonatal body weights, at postnatal days (PNDs) 2, 15 and 30 were reduced in a dose-dependent manner, with LOF-induced reduction twice that of CLON. No significant differences were obtained on negative geotaxis, an auditory startle test, or a series of swimming immobilization tests across the periadolescent period. A series of activity measures carried out on PND 12, 14, 16 and 18 showed minor differences in the high dose LOF male animals, but not in any of the other drug-treated groups.
Pizzi
W J
WJ
Department of Psychology, Northeastern Illinois University, Chicago 60625.
Ali
S F
SF
Holson
R R
RR
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects; D013550:Swimming
D000959:Antihypertensive Agents; D003000:Clonidine; C025655:lofexidine