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.