Prenatal exposure to cocaine selectively disrupts motor responding to D-amphetamine in young and mature rabbits.
Acute administration of D-amphetamine probed the functional effects of prenatal exposure to cocaine on the integrity of monoaminergic systems in preweanling (48-56 days old) and adult (> or = 140 days old) Dutch belted rabbits. D-Amphetamine sulfate (0, 0.3, 1.0, 3.3 and 6.0 mg/kg, s.c.) produced equivalent dose-related reductions in food intake in 180 day-old rabbits that had been exposed in utero on gestational days 8-29 to cocaine or saline. Intrauterine exposure to cocaine also did not alter the incidence of exploratory behaviors stimulated by D-amphetamine during the anorexia test. In contrast, however, prenatal cocaine virtually eliminated stereotyped head bobbing elicited by the highest dose of D-amphetamine. When responses to 5.0 mg/kg D-amphetamine were measured during a 90-min open field test, prenatal cocaine prevented head bobbing in preweanling rabbits and reduced this behavior by 92% in 140 day-old adults. Prenatal cocaine also diminished the intensity of other motor responses in the open field in the adults but not in preweanlings. In normal rabbits, the D1 antagonist R(+)-SCH 23390 (0.01 mg/kg, s.c.) blocked D-amphetamine-induced head bobbing. Thus, prenatal exposure to cocaine produces an early and persistent deficit in behavioral responding to a high dose of D-amphetamine. The deficit is especially selective at the time of weaning, broadens to affect more motor behaviors with maturation and may reveal impaired D,-mediated dopaminergic neurotransmission in the brain.
Simansky
K J
KJ
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, USA.
Kachelries
W J
WJ
D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits
D000661:Amphetamine; D003042:Cocaine