title: Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical Faculty University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia. sikiric@mef.hr.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
authors.forename: Nikola
authors.initials: N
authors.lastname: Jelovac
authors.forename: Andjelka
authors.initials: A
authors.lastname: Jelovac-Gjeldum
authors.forename: Goran
authors.initials: G
authors.lastname: Dodig
authors.forename: Mario
authors.initials: M
authors.lastname: Staresinic
authors.forename: Tomislav
authors.initials: T
authors.lastname: Anic
authors.forename: Ivan
authors.initials: I
authors.lastname: Zoricic
authors.forename: Davor
authors.initials: D
authors.lastname: Rak
authors.forename: Darko
authors.initials: D
authors.lastname: Perovic
authors.forename: Gorana
authors.initials: G
authors.lastname: Aralica
authors.forename: Gojko
authors.initials: G
authors.lastname: Buljat
authors.forename: Ingrid
authors.initials: I
authors.lastname: Prkacin
authors.forename: Martina
authors.initials: M
authors.lastname: Lovric-Bencic
authors.forename: Jadranka
authors.initials: J
authors.lastname: Separovic
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rucman
authors.forename: Marijan
authors.initials: M
authors.lastname: Petek
authors.forename: Branko
authors.initials: B
authors.lastname: Turkovic
authors.forename: Tihomil
authors.initials: T
authors.lastname: Ziger
authors.forename: Alenka
authors.initials: A
authors.lastname: Boban-Blagaic
authors.forename: Vlado
authors.initials: V
authors.lastname: Bedekovic
authors.forename: Ante
authors.initials: A
authors.lastname: Tonkic
authors.forename: Slaven
authors.initials: S
authors.lastname: Babic
mesh_terms: 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
chemical_list: D015259:Dopamine Agents; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D000661:Amphetamine