Prenatal exposure to imipramine alters early behavioral development and beta adrenergic receptors in rats.
Offspring of rats exposed to water or 15 mg/kg/dy of imipramine (IMI) on gestational day 8 through 20 were examined for behavioral and neurochemical development. IMI-treated mothers gained significantly less weight during pregnancy, but the percentage giving birth, length of gestation and litter size were unaffected. Body weights of IMI-exposed offspring were significantly lower than controls until postnatal day 14 and brain weights were lower until day 30. In IMI-exposed pups, eye-opening occurred significantly earlier, development of the surface righting reflex was delayed and development of negative geotaxis was altered. Hypothalamic levels of noradrenaline and adrenaline were unchanged in IMI pups at 7, 14 and 30 days, but dopamine levels, unaffected at 7 and 14 days, were significantly lower than controls at 30 days. The number of cortical beta adrenergic receptors, measured by [3H]dihydroalprenolol binding, was significantly decreased by 18.7% at 14 days and 9.1% at 30 days. Affinity for binding was increased at 30 days. Brain levels of IMI and its metabolite desmethylimipramine were detectable in newborns prenatally exposed to IMI and desmethylimipramine/IMI ratios were 1.8 times those found in adults. The results indicate that prenatal exposure to IMI produces behavioral and neurochemical consequences lasting well past cessation of drug exposure.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D005260:Female; D006128:Growth / Q000187:drug effects; D007099:Imipramine / Q000378:metabolism / Q000494:pharmacology*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D007099:Imipramine