Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenalactivity

Rationale: Gabolysat PC60 is a fish protein hydrolysate with anxiolytic pro perties commonly used as a nutritional supplement. Objective: The diazepam- like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. Methods: The activity of the pituitary-adrenal axis, measured by plasma levels of adrenocorticotr opic hormone (ACTH) and corticosterone (B) of the sympathoadrenal complex, measured by circulating levels of noradrenaline (NA) and adrenaline (A), an d the gamma aminobutyric acid !GABA) content in the hippocampus and the hyp othalamus were investigated in male rats which received daily, by an intrag astric feeding tube, for 5 days running either diazepam (1 mg/kg) or PC60 ( 300 or 1200 mg/kg). Controls received only solvent (carboxymethylcellulose 1%. Six hours after the last force-freding. the rats were subjected to 3 mi n ether inhalation or 30 min restraint and killed by decapitation 30 min af ter ether stress or at the end of restraint. Results: Baseline plasma level s of ACTH, B, NA and A were not affected by either diazepam or PC60. Both e ther- and restraint-induced release of ACTH, but not B, were similarly and drastically reduced by diazepam and PC60 ( 1200 mg/kg). Both diazepam and P C60 (1200 mg/kg) deleted restraint-induced NA and A increases. Both treatme nts also reduced the ether-induced rise of A. Basal levels of GABA were sig nificantly increased in both the hippocampus and the hypothalamus in PC60-t reated rats and only in the hippocampus in diazepam-treated ones. In contro ls, ether inhalation as well as restraint increased GABA content of these t wo brain structures. In contrast, such stress procedures performed in PC60- treated rats reduced GABA content slightly in the hippocampus but significa ntly in the hypothalamus. In diazepam-treated rats, GABA content of the hyp othalamus was unaffected by stresses but that of the hippocampus was slight ly decreased. Conclusions: Present data suggest diazepam-like effects of PC 60 on stress responsiveness of the rat pituitary adrenal axis and the sympa thoadrenal activity as well as GABA content of the hippocampus and the hypo thalamus under resting and stress conditions. These effects of PC60 agree w ith anxiolytic properties of this nutritional supplement, previously report ed in both rats and humans.