Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances.
OBJECTIVE
To investigate the effect of pentadecapeptide BPC 157 on chronic exposure to amphetamine in rats, particularly the changes commonly referred in chronic amphetamine studies as tolerance (lesser grade of stereotyped behavior, without increased excitability) and reverse tolerance (ie, prominent stereotyped behavior and heightened startle response upon late amphetamine challenges).


METHODS
After initial application (initial single dose-regimen), amphetamine (10 mg/kg,ip) was given once daily till d 5 (continuous administration-regimen), and thereafter on d 8, 16, and 46 (intermittent administration regimen). Fo r stereotyped behavior and heightened startle response the observation period was 120 min after amphetamine application, and each animal was observed for 10 s in 5 min intervals. Pentadecapeptide BPC 157 (10 microg/kg or 10 ng/k g, ip) or saline (5.0 mL/kg, ip) were given only at the beginning of the experiment, simultaneously with the initial dose of amphetamine.


RESULTS
In relation to applied initial-single/continuous/intermittent amphetamine applications regimen, the control amphetamine rats throughout the experiment showed the changes in stereotyped behavior and heightened startle response, increment or decrement, commonly explained in chronic amphetamine studies as tolerance and reverse tolerance. After t he initial application of the amphetamine, the higher BPC 157 dosage apparently attenuated the stereotyped behavior, while the lower dosage of BPC 157 did not reach a statistical significance. Considering the forthcoming amphetamine challenges, in the rats initially treated with pentadecapeptide BPC 157, either 10 microg- or 10 ng-dose, at the time of the first application of amphetamine, the stereotyped behavior remains to be attenuated after all additional amphetamine challenges (on d 2-5, 8, 16, and 46). This attenuation was not limited to stereotyped behavior only. After the initial application of the amphetamine the heighten ed startle response was also apparently mitigated in rats receiving the BPC 157 dosage, either higher or lower. Later, confronted with the forthcoming amphetamine challenges, they showed apparently less abnormal excitability at all tested points.


CONCLUSIONS
In summary, gastric pentadecapeptide BPC 157 (ie, both microg- and ng-BPC 157 regimens) attenuated chronic amphetamine disturbances. This effect was present throughout the observation period at a statistically significant level. Therefore, it seems that this gastric pentadecapeptide BPC 157 has a modulatory effect on dopamine system, and it could be used in chronic amphetamine disturbances.
Sikiric
Predrag
P
Department of Pharmacology, Medical Faculty University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia. sikiric@mef.hr.
Jelovac
Nikola
N
Jelovac-Gjeldum
Andjelka
A
Dodig
Goran
G
Staresinic
Mario
M
Anic
Tomislav
T
Zoricic
Ivan
I
Rak
Davor
D
Perovic
Darko
D
Aralica
Gorana
G
Buljat
Gojko
G
Prkacin
Ingrid
I
Lovric-Bencic
Martina
M
Separovic
Jadranka
J
Seiwerth
Sven
S
Rucman
Rudolf
R
Petek
Marijan
M
Turkovic
Branko
B
Ziger
Tihomil
T
Boban-Blagaic
Alenka
A
Bedekovic
Vlado
V
Tonkic
Ante
A
Babic
Slaven
S
D000661:Amphetamine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000818:Animals; D015259:Dopamine Agents / Q000009:adverse effects; D004347:Drug Interactions; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D015259:Dopamine Agents; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D000661:Amphetamine