Anxiolytic‐like effects and safety profile of a tryptic hydrolysate from bovine alpha s1‐casein in rats

Abstract

The anxiolytic activity and adverse benzodiazepine-like effects of a bovine alpha s1-casein tryptic hydrolysate (CH) were evaluated. The effects of CH orally administered at doses of 5 and 15 mg/kg were compared with those of diazepam (DZ) at 3 mg/kg in the conditioned defensive burying test. Rats treated either with CH at 15 mg/kg or with DZ showed a decrease in anxiety. A drug-related difference was observed in terms of duration, as the anxiolytic-like action of CH was maintained after 7 days with twice-daily administration, whereas that of DZ was not. CH and DZ were then evaluated for their potential effects on memory in a passive avoidance paradigm. CH-treated rats had significantly longer latencies before entering the dark compartment where they were previously delivered a shock, indicating better retention relative to DZ-treated rats. In the final test, CH and DZ were evaluated for place preference, an index of the possible addictive potential of these substances. DZ-treated rats spent more time in the compartment associated with drug exposure than control rats. This effect was not found in CH-treated rats. Thus, CH did not display side effects associated with DZ, despite its affinity for gamma-aminobutyric acid(A) (GABA(A)) receptors. Specific linking of CH on GABA(A) receptor function involved in anxiolysis, but not on that implied in memory-impairing effects, may be hypothesized to explain its specific activity. This profile might render it advantageous for nutritional purposes.