A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine. | Pepdox
A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine.
Tests BPC 157 (prophylactic and therapeutic regimens) against amphetamine-induced stereotypy, startle response, and haloperidol-induced dopamine supersensitivity in rats and mice. BPC 157 markedly attenuated stereotypy and acoustic startle during acute amphetamine, and reversed peak amphetamine excitability when given therapeutically. Most critically, co-administration of BPC 157 with haloperidol almost completely reversed the subsequent behavioral supersensitivity to amphetamine challenge (1–10 days later). Foundational evidence establishing BPC 157's interaction with the dopamine system as both pre- and post-synaptic modulator.
Abstract
BACKGROUND: A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy.
METHODS: We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg i.p.).
RESULTS: There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect.
CONCLUSIONS: An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.