Sikiric Predrag, Jelovac Nikola, Jelovac-Gjeldum Andjelka, Dodig Goran, Staresinic Mario, Anic Tomislav, Zoricic Ivan, Rak Davor, Perovic Darko, Aralica Gorana, Buljat Gojko, Prkacin Ingrid, Lovric-Bencic Martina, Separovic Jadranka, Seiwerth Sven, Rucman Rudolf, Petek Marijan, Turkovic Branko, Ziger Tihomil, Boban-Blagaic Alenka, Bedekovic Vlado, Tonkic Ante, Babic Slaven
Department of Pharmacology, Medical Faculty University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia.
Acta Pharmacol Sin. 2002 May;23(5):412-22.
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).
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.
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.
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.
研究十五肽BPC 157对大鼠长期暴露于苯丙胺的影响，特别是在慢性苯丙胺研究中通常提到的耐受性变化（刻板行为等级较低，兴奋性未增加）和反向耐受性变化（即，后期苯丙胺激发时明显的刻板行为和增强的惊吓反应）。
在首次给药（初始单剂量方案）后，每天一次给予苯丙胺（10mg/kg，腹腔注射），持续至第5天（连续给药方案），此后在第8、16和46天给予（间歇给药方案）。对于刻板行为和增强的惊吓反应，观察期为苯丙胺给药后120分钟，每隔5分钟对每只动物观察10秒。十五肽BPC 157（10μg/kg或10ng/kg，腹腔注射）或生理盐水（5.0mL/kg，腹腔注射）仅在实验开始时与苯丙胺初始剂量同时给予。
相对于所应用的初始单剂量/连续/间歇苯丙胺给药方案，整个实验过程中对照苯丙胺大鼠表现出刻板行为和增强的惊吓反应的变化，即增加或减少，在慢性苯丙胺研究中通常解释为耐受性和反向耐受性。在首次给予苯丙胺后，较高剂量的BPC 157明显减弱了刻板行为，而较低剂量的BPC 157未达到统计学意义。考虑到即将进行的苯丙胺激发，在首次给予苯丙胺时最初用十五肽BPC 157（10μg或10ng剂量）治疗的大鼠中，在所有额外的苯丙胺激发后（第2 - 5、8、16和46天）刻板行为仍减弱。这种减弱不仅限于刻板行为。在首次给予苯丙胺后，接受较高或较低剂量BPC 157的大鼠中增强的惊吓反应也明显减轻。之后，面对即将进行的苯丙胺激发，它们在所有测试点的异常兴奋性明显较低。
总之，胃十五肽BPC 157（即μg - BPC 157和ng - BPC 157方案）减弱了慢性苯丙胺干扰。在整个观察期内这种作用在统计学上具有显著意义。因此，看来这种胃十五肽BPC 157对多巴胺系统具有调节作用，可用于慢性苯丙胺干扰。
