Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances.
Abstract
AIM: 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.
CONCLUSION: 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.
Keywords:
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.
CONCLUSION: 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.