Differential effects of prenatal exposure to cocaine and amphetamine on growth parameters and morphometry of the prefrontal cortex in the rat.
The purpose of this study was to investigate the differential effects of prenatal exposure to psychostimulants, e.g., cocaine or amphetamine, on basic growth parameters and morphometry of the medial prefrontal cortex of the rat. A group of pregnant Wistar rats was given 60 mg/kg body weight/day of cocaine hydrochloride and another group 10 mg/kg body weight/day of d-amphetamine sulfate, subcutaneously, from gestational days 8 to 22. Control groups of pregnant rats were pair-fed; litters were culled to eight pups (4 males and 4 females) weighed every other day until postnatal day 30 and every week until day 90. The body weight growth patterns modelled by a Gompertz curve were different in rats prenatally exposed to the two psychostimulants. Rats exposed to amphetamine had on average a slower growth than those exposed to cocaine, reaching an identical estimated adult weight. Allometric relationships between forebrain and body weight and cerebellum and body weight were described by two distinct postnatal growth phases that are different among the experimental groups. In the comparison of the two psychostimulants the relative cerebellum/body growth is lower in the offspring of the cocaine group than in the amphetamine group between PND14-PND30; between PND30-PND90 the relative growth rate is considerably higher in the offspring of the cocaine dams compared to that of the amphetamine dams. Groups of perfused animals were selected at postnatal days 14 and 30 to analyze the morphometric organization of the medial prefrontal cortex. In serial celloidin sections the volumes of the prefrontal cortex were determined; the number of neurons per unit volume of reference area was calculated using the stereological technique of the disector. The changes found in the morphometric parameters show a catch-up at postnatal day 30 of the "increased" density of neurons of the medial prefrontal cortex found at postnatal day 14. These data show differential growth patterns of offspring from cocaine- and amphetamine-exposed rats; a delayed development in the achievement of normal morphometric parameters of neurons in the prelimbic subarea of the medial prefrontal cortex occurs in the prenatally amphetamine-exposed offspring at early ages, and a catch-up is found after the first month of life. Complementary studies are needed to assess whether these changes have functional implications in the rats exposed prenatally to psychostimulants.
Tavares
M A
MA
Institute for Molecular and Cellular Biology (IBMC), University of Porto, Portugal.
Silva
M C
MC
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D008098:Litter Size; D008297:Male; D009474:Neurons / Q000187:drug effects; D009929:Organ Size; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D000661:Amphetamine; D003042:Cocaine