Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 265

P08-007 - Evaluation of the mechanism of action of LACTIUM®, a milk hydrolysate enriched in alpha-casozepine with anxiolytic properties

Monday, Jun 11
8:00 AM – 3:00 PM



Objective: Benzodiazepine site of GABAA receptor is a major target for the modulation of anxiety in both animals and humans. The objective is to evaluate whether Flumazenil, a benzodiazepine antagonist, inhibited the anxiolytic effect of Lactium® in the conditioned defensing burying (CDB) test of anxiety in rat.


Methods: Six groups of rats were studied (n=14). The first treatment was administered 80 minutes before testing. Each rat received either Flumazenil (FLU; 10 mg/kg) or placebo (negative control) by intraperitoneal injection (I.P).
Then 60 minutes before testing, a second treatment of Lactium® (15 mg/kg), Diazepam (benzodiazepine agonist; 3 mg/kg) or placebo (negative control) was given to each of the rats by oral administration (P.O.).
Each rat was tested for 5 minutes in the CDB test, an experimental situation in which rats bury an anxiogenic probe with the sawdust present on the floor. For each group, the global score of anxiety (GSA) was calculated from the measurement of the following behaviors: duration of probe-burying, number of head stretches towards the probe, number of approach/flight sequences towards the probe.
The statistical analysis used is: test of Kruskal-Wallis following the test of Mann-Whitney.


Results: The administration of Lactium® at 15mg/kg P.O. 60 minutes before the CDB test induced a significant decrease of GSA of the rats, which confirms the anxiolytic effect of Lactium®.
The administration of FLU at 10mg/kg I.P. 20 min before the administration of Diazepam or Lactium® blocked their respective anxiolytic effects, but had no anxiogenic effect when injected alone. (Figure 1.)
This indicates that Lactium® exerts its anxiolytic activity via the benzodiazepine site of GABAA receptor, similarly to benzodiazepines like Diazepam.

Conclusion
The anxiolytic effect of Lactium® is mainly linked to the modulation of GABA system via benzodiazepine site of GABAA receptor. The way that Lactium® components reach the brain remains to be evaluated.




Funding Source: INGREDIA S.A.
Figure 1: Graph of global anxiety score

CoAuthors: Nicolas Violle – Etap-Lab; Sylvain Denis – Clermont Auvergne University; MOnique ALRIC – Clermont Auvergne University ; Sylvain Denis – Clermont Auvergne University; Monique Alric – Clermont Auvergne University; Alain Baniel – INGREDIA S.A.; Audrey Romelard – INGREDIA S.A.; Alain Baniel – Ingredia S.A.

Audrey Boulier

Scientific and innovation Manager Bioactives and Nutrition
Ingredia S.A.
Arras, Nord-Pas-de-Calais, France