Naslov
Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances

Autori
Sikirić, Predrag ; Jelovac, Nikola ; Jelovac-Gjeldum, Andjelka ; Dodig, Goran ; Starešinić, Mario ; Anić, Tomislav ; Zoričić, Ivan ; Perović, Darko ; Aralica, Gorana ; Buljat, Gojko ; Prkačin, Ingrid ; Lovrić- Benčić, Martina ; Šeparović, Jadranka ; Seiwerth, Sven ; Ručman, Rudolf ; Petek, Marijan ; Turković, Branko ; Ziger, Tihomil ; Boban-Blagaić, Alenka ; Bedeković, Vlado ; Tonkić, Ante ; Babić, Slaven

Izvornik
Acta pharmacologica Sinica (1671-4083) 23 (2002), 5; 412-422

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
gastric pentadecapeptide BPC 157 ; chronic amphetamine ; stereotyped behavior ; heightened startle response ; attenuation

Sažetak
A gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W. 1419, coded BPC-157, with mucosal protective, wound healing and anti-inflammatory effect, interacting with NO, and somatosensory neurones system, and a peculiar high stability in gastric juice, was recently shown to block stereotypy and heightened startle responses, produced by an application of dopamine agonist amphetamine. Therefore, the next focus was to see the effect on chronic exposure to amphetamine in rats (i.e., 10 mg/kg b.w. i.p.., once time daily for five subsequent days, and thereafter at the day 8, 16 and 46). Considering the prominent effect of single application of pentadecapeptide BPC 157 (10 ľg/kg or 10 ng/kg b.w. i.p.) or saline (5.0 ml/kg i.p.) on both development as well as reversal of amphetamine stereotypy and heightened startle response, pentadecapeptide BPC 157 (10 ľg/kg or 10 ng/kg b.w. i.p.) or saline (5.0 ml/kg i.p.) were given only at the beginning of the experiment, simultaneously with the initial dose of the amphetamine. In relation initial-single/repeated- intermittent application(s), the changes in stereotyped behavior and heightened startle response, increment or decrement, noted in control amphetamine rats are in line with the changes commonly referred in chronic amphetamine studies as tolerance (lesser grade of stereotyped behavior, without increased excitability) and reverse tolerance (i.e., prominent stereotyped behavior and heightened startle response upon late amphetamine challenges). After the initial application of the amphetamine, in rats receiving the higher BPC 157 dosage the stereotyped behavior was apparently attenuated, while in rats receiving the lower dosage of BPC 157 statistical significance was not found. These differences were present throughout the observation period (120 minutes after amphetamine application, and each animal was observed for 10 seconds in 5 minutes intervals) and were statistically significant at all the observed intervals. Considering the forthcoming amphetamine challenges, in the rats initially protected with pentadecapeptide BPC 157 at the time of the first application of amphetamine, the stereotyped behavior remains to be attenuated after all additional amphetamine challenges (at the day 2-5, 8, 16, and 46). Moreover, in these days, a significant attenuation appeared also in the rats that had been treated with the lower dose of the pentadecapeptide BPC 157 at the time of the fist amphetamine application. After the initial application of the amphetamine, in rats receiving the BPC 157 dosage, either higher or lower, the heightened startle response was apparently mitigated. These differences were present throughout the observation period and were statistically significant at all the observed intervals. Considering the forthcoming amphetamine challenges, in the rats initially protected with pentadecapeptide BPC 157 at the time of the first application of amphetamine, they showed apparently less abnormal excitability at all tested points. Like in the rats damaged with only first application of amphetamine, this mitigation was consistently evident in both ug- and ng-BPC 157 regimens. Thus, taking together these data, it seems that this pentadecapeptide has a modulatory effect on dopamine system, and it could be used in chronic amphetamine disturbances.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA