Proproten in Alleviating the Anticipatory Anxiety: Results of Experimental Study

Abstract

Proceedings of the 9th International Multidisciplinary Conference «Stress and Behavior» Saint-Petersburg, Russia, 16–19 May 2005.Proproten, ultra-low doses of antibodies to brain S-100 protein for oral use (orally disintegrating tablets), have been successfully marketed in Russia since 1999 as a treatment option for alcohol withdrawal. In the earlier experimental studies, proproten was shown to possess a unique psychotropic profile including anxiolytic, anti-depressant and neuroprotective properties. The anticipatory anxiety of pain related to a medical procedure is one of the main problems of public health. The anticipation of pain is perhaps the biggest deterrent to the acceptance of professional dental care. The anticipation of pain phenomenon has been documented by an impressive number of clinical and experimental studies. Recently, research interest has moved to the effects of pain anticipation and the possibility of preventing them. This presented research was aimed at studying the influence of proproten on conditioned anxiety in the «anticipation of pain» test.Methods. Adult white outbread male rats (200–220 g) were exposed to an uncontrollable stressful condition (10 inescapable electric foot shocks, 0.45 mA, duration of 1 s in a 2 s interval) in a stainless steel grid floor chamber («Lafayette Instrument Co», USA). After the procedure the animals were taken out of the chamber and left in a cage given free access to water and food. The next day, in a 24-hour period, the rats were again placed in the chamber where they had experienced earlier foot shock for 5 min; although the painful stimuli were not delivered, the rats were stressed. The conditioned emotional response without and under provocation (a pencil was pointed to the rat’s head) was assessed during 4 min. The rats received 2.5 ml/kg of proproten i.g. (n = 20) or vehicle (n = 20) 30 min before they were placed in the chamber for the second time. Diazepam (1 mg/kg) was used as a reference drug.Results and discussions. The rats placed in the chamber where the electric shock had been delivered earlier showed a strong response to stress. The freezing reaction was found in 45 % of rats (55 % — under provocation), 35 % of animals were active (40 % — under provocation), while only 20 % of rats showed exploratory behavior (5 % — under provocation). The incidence of defecation, urination, and tachypnoe under the stressful conditions was rather high (Table 1). Proproten as well as diazepam greatly reduced the number of stress-induced events. Under stressful conditions, the proproten-treated animals were active 3 times as often as the diazepam-treated ones (4 times — under provocation). Notably, the anti-stress effect of proproten was more pronounced when the stress of anticipation of pain was aggravated by additional provocation. The incidence of freezing was 3 times lower in the group given proproten compared with diazepam (Table 1).Conclusions. In the «anticipation of pain» test, the anti-stress activity of proproten was equal to that of diazepam. Proproten exerted influence on both the rats with active, aggressive behavior and on the animals freezing in the response to the stress, while diazepam mostly modified the active stress-related behavior. In conclusion, proproten was shown to meet the medical needs of the patients who are about to undergo medical procedures and show anticipatory anxiety. Randomized clinical trials are to be conducted to confirm the above-mentioned activity in clinical practice