The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating

Abstract

Converging evidence from preclinical and clinical studies suggest that oxytocin has therapeutic potential for schizophrenia and other neuropsychiatric disorders. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating, an important brain function involved in filtering environmental information. We previously demonstrated that systemically administered oxytocin reversed psychostimulant-induced PPI deficits in rats suggesting that oxytocin can produce antipsychotic-like central effects. That finding was supported by a recent trial in humans, which found that intranasal oxytocin reduced symptoms of schizophrenia. The goal of this study was to extend this line of investigation by testing the effects of oxytocin, and a structural analog of oxytocin, carbetocin, on nonpharmacological deficits in PPI. In experiment 1, Brown Norway (BN) rats, a rat strain that has naturally low PPI, were given either saline or one of three doses of oxytocin (0.04 - 1.0 mg/kg, sc). In experiment 2, BN rats were given either saline, one of three doses of carbetocin (0.04 - 1.0 mg/kg) or oxytocin (1 mg/kg). PPI and acoustic startle response (ASR) of rats were tested. Oxytocin significantly increased PPI (P < 0.01) and decreased ASR levels (P < 0.01) in BN rats in a dose-dependent fashion. In contrast, carbetocin had no effect on PPI levels or ASR. The facilitation of BN PPI by oxytocin is similar to what we have previously observed with clozapine and thus further supports oxytocin having antipsychotic properties. In contrast to oxytocin, our data do not support the use of carbetocin as an antipsychotic drug.

Peripherally administered oxytocin modulates latent inhibition in a manner consistent with antipsychotic drugs

“…For example, peripherally administered OT alters various aspects of social behavior and fear in rodents [4,5]. Similarly, our laboratory has demonstrated that subcutaneously (SC) administered OT enhances prepulse inhibition of the startle reflex (PPI), a centrally mediated index of sensorimotor gating an important feature of normal information processing [6,7], consistent with OT activity in the brain.…”

“…Peripherally administered OT enhances PPI deficits induced by psychotomimetic drugs and PPI deficits naturally exhibited in the Brown Norway (BN) rat strain [6,7]. The facilitation of reduced PPI is consistent with the effects of antipsychotic drugs (APDs) and suggests that OT may have therapeutic potential for schizophrenia.…”

“…For example, administration of dopamine enhancing drugs such as amphetamine concomitant with conditioning disrupts LI. In contrast, the Brown Norway (BN) rat has been found to exhibit low LI [15], in addition to other schizophrenia relevant phenotypes such as low PPI [7,16]. …”

International experience with pabal (carbetocin) for the prevention and treatment of postpartum hemorrhage

“…Подобно окситоцину, пабал (карбето-цин) избирательно связывается с рецепторами окситоци-на в гладкой мускулатуре матки, стимулирует ритмичные сокращения матки, увеличивает частоту схваток и повы-шает тонус маточной мускулатуры [36]. В послеродовой матке пабал (карбетоцин) увеличивает скорость и силу спонтанных маточных сокращений.…”

“…Эффективность различных доз пабала при внутри-венном и внутримышечном использовании оценивали по Российский вестник акушеРа-гинеколога 4,2016 данным записей токографии в течение 24-48 ч после срочных вагинальных родов у 40 женщин [36]. После од-нократного внутривенного болюсного введения 8-30 мкг или внутримышечного -10-70 мкг карбетоцина (пабал) отмечали тетаническое сокращение матки в течение 2 мин.…”