Release of [3H]norepinephrine: alteration by early developmental exposure to diazepam.
The effect of prenatal exposure to diazepam (over gestational days 13-20) on the release of tritiated norepinephrine [( 3H]NE) from selected brain regions was analyzed to determine mechanisms whereby such exposure could disrupt functioning in specific NE neurons, as previously observed. Pregnant rats were administered diazepam (DZ) once daily at doses of 1.0, 2.5 or 10.0 mg/kg and the offspring studied as adults at 70-90 days of age and during development at 14, 21, 35 and 56 days of age. Release of [3H]NE was measured during in vitro incubation using 25 mM potassium as the depolarizing stimulus. As noted previously, prenatal exposure to DZ induced an effect only on NE neurons innervating the hypothalamus, sparing the NE innervation to the hippocampus and cerebellum. Prenatal exposure to DZ had no effect on the depolarized release of [3H]NE in the hypothalamus until after 35 days of age, a developmental pattern previously observed with respect to endogenous NE levels. In adult rat offspring, however, the depolarization-induced release of [3H]NE from the hypothalamus decreased 28%, 32% and 64% (relative to uninjected control values) in animals prenatally exposed to DZ at 1.0, 2.5 or 10 mg/kg/day respectively. Concurrent exposure of the pregnant dam to benzodiazepine antagonists (Ro 15-1788 or ethyl-beta-carboline-3-carboxylate) prevented the effects of DZ (2.5 mg/kg/day) on [3H]NE release, demonstrating again the importance of the benzodiazepine binding site to the effects induced by the early DZ exposure. The initial accumulation of the [3H]NE was not altered by the prenatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D011963:Receptors, GABA-A; D003975:Diazepam; D009638:Norepinephrine; D010646:Phentolamine