Effects of lorazepam on the properties of brain polysomes.
This study determined the effects of acute administration of lorazepam (LRZ) on brain protein synthesis by examining the translational abilities of polysomal RNA under in vitro conditions compared to those produced by the CNS depressants, ethanol and pentobarbital. Lorazepam (2 mg/kg body weight), ethanol (4 g/kg body weight) or pentobarbital (40 mg/kg body weight) were given orally to 6-week old male Sprague-Dawley rats. Control groups were either untreated or received the vehicle sesame seed oil orally. The measurement of rectal temperature in each group before (baseline) and 60 min after drug administration showed no change in body temperature in the control or LRZ treated groups but there was a significant temperature drop in the ethanol and pentobarbital group. After 60 min of drug administration, experimental groups when compared to the controls showed significant inhibitions in the translational activities of the cerebral polysomes. The inhibition was most pronounced with polysomes from the LRZ treated group and was consistently observed over a 60 min time period. The findings suggest polysomal translation as one of the major sites of action of LRZ which is independent of changes in body temperature as compared to ethanol and pentobarbital. Since protein synthesis is known to play a key role in learning and memory, the observed inhibitory effects of LRZ may explain its interference with memory consolidation observed under experimental and clinical conditions.
Tewari
S
S
Department of Psychiatry and Human Behavior, College of Medicine, University of California, Irvine.
Gottschalk
L A
LA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011132:Polyribosomes / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D010424:Pentobarbital; D008140:Lorazepam