Anxiolytic-like effects and safety profile of a tryptic hydrolysate from bovine alpha s1-casein in rats.
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.
Messaoudi
Michaël
M
ETAP-Applied Ethology, Technopôle de Nancy-Brabois, 13 rue du Bois de la Champelle, 54500 Vandoeuvre-lès-Nancy, France. etap@etap-lab.com
Lalonde
Robert
R
Schroeder
Henri
H
Desor
Didier
D
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001007:Anxiety / Q000188:drug therapy*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D002417:Cattle; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D014151:Anti-Anxiety Agents; D002364:Caseins; D011963:Receptors, GABA-A; C475729:casein hydrolysate; D003975:Diazepam