Influence of sedatives on stress-induced trans-synaptic induction of tyrosine hydroxylase.
Rats were exposed to combined enforced swimming and cold stress in order to investigate the influence of the sedative compounds 2-(2-oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), phenobarbital, and diazepam on stress-induced changes in cyclic adenosine 3',5'-phosphate (cAMP) and trans-synaptic induction of tyrosine hydroxylase (TH) in adrenal glands. Pretreatment with supidimide at greater than or equal to 150 mg/kg suppresses the early poststress rise in cAMP and the delayed TH induction. Phenobarbital at 75 mg/kg slightly inhibits the cAMP increase, but does not significantly interfere with TH induction. Diazepam already at 5 mg/kg completely blocks the stress-induced increase of cAMP, but leaves the TH induction unchanged at dosages up to 20 mg/kg. It is concluded that the stress-induced rise in adrenal cAMP and the trans-synaptic induction of TH are rather coincidental than causally related. Suppression of TH induction by supidimide appears to be a peculiarity of this compound not strictly related to its sedative potency.
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D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000201:enzymology* / Q000378:metabolism; D013550:Swimming; D013569:Synapses / Q000201:enzymology*; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D006993:Hypnotics and Sedatives; D013792:Thalidomide; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D006152:Cyclic GMP; C027948:supidimide; D003975:Diazepam; D010634:Phenobarbital