title: Maternal methadone administration: deficit in development of alpha-noradrenergic responses in developing rat brain as assessed by norepinephrine stimulation of 33Pi incorporation into phospholipids in vivo.
abstract: The effects of perinatal methadone exposure on the development of noradrenergic responses in the brain were examined by assessing the ability of intracisternally administered norepinephrine to stimulate 33Pi incorporation into phospholipids in vivo; the effect of norepinephrine is mediated by alpha1-receptors juxtaposed to noradrenergic nerve terminals. Although there was no difference in basal (unstimulated) incorporation of 33Pi, a deficit in norepinephrine-induced stimulation of incorporation was found throughout the preweaning period in offspring of dams treated daily with methadone beginning in midgestation. This effect was not seen when methadone was given during the postnatal period. Since perinatal methadone exposure also delays development of presynaptic catecholaminergic nerve terminals in the brain, these results support the view that perinatal exposure to methadone depresses overall central noradrenergic synaptic function; however, the effects on presynaptic development and on receptor-mediated responses appear to be separable in that they display differences in the critical age periods of sensitivity to perturbation by the drug.
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008431:Maternal-Fetal Exchange; D008691:Methadone / Q000633:toxicity*; D009638:Norepinephrine / Q000494:pharmacology; D010743:Phospholipids / Q000096:biosynthesis; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
chemical_list: D010743:Phospholipids; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D008691:Methadone; D009638:Norepinephrine