Precipitated diazepam withdrawal elevates noradrenergic metabolism in primate brain.
Following treatment for seven days with diazepam (2.0 mg/kg i.m., b.i.d.), administration of the benzodiazepine receptor antagonist RO 15-1788 (5 mg/kg) induced a severe withdrawal syndrome in vervet monkeys which included tremors, vomiting, vocalizations, chewing, and piloerection. Brain concentrations of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly higher in the precipitated withdrawal group than in the diazepam plus vehicle control group. Administration of RO 15-1788 without prior diazepam treatment had no effect on brain MHPG, nor did it produce withdrawal behaviors, but did produce an increase in the frequency of scratching. These results raise the possibility that increased central noradrenergic activity serves a role in benzodiazepine withdrawal similar to the role hypothesized for noradrenergic activity in opiate withdrawal.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003975:Diazepam / Q000009:adverse effects*; D005260:Female; D005442:Flumazenil; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000032:analysis; D009294:Narcotics / Q000009:adverse effects; D009638:Norepinephrine / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D001570:Benzodiazepinones; D009294:Narcotics; D005442:Flumazenil; D008734:Methoxyhydroxyphenylglycol; D003975:Diazepam; D009638:Norepinephrine