Khani Fatemeh, Pourmotabbed Ali, Hosseinmardi Narges, Nedaei Seyed Ershad, Fathollahi Yaghoub, Azizi Hossein
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jun 8;116:110532. doi: 10.1016/j.pnpbp.2022.110532. Epub 2022 Feb 8.
Opioid exposure during adolescence, a crucial period of neurodevelopment, has lasting neurological and behavioral consequences and affects the cognitive functions in adulthood. This study investigated the effects of adolescent morphine exposure in spatial learning and memory and synaptic plasticity of the CA1 area of the dorsal hippocampus. Adolescent Wistar rats received increasing doses of morphine for 1, 5, and 10 days. Acute morphine group was injected 2.5 mg/kg morphine for 1 day, subchronic morphine group for 5 days, with an increasing dose of 2.5 mg/kg and reached to the dose of 12.5 mg/kg and chronic morphine group for 10 days that began with an increasing dose of 2.5 mg/kg and reached to the dose of 25 mg/kg. Then after 25 days and reaching adulthood, spatial learning and memory were evaluated via the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of dorsal hippocampal plasticity in adult rats by in vitro field potential recordings. Subchronic and chronic adolescent morphine exposure impaired spatial learning and memory in the MWM test. Baseline synaptic responses in the chronic morphine group were increased and long-term potentiation (LTP) impaired in the CA1 area in subchronic and chronic morphine groups. In adulthood, the slope of the field excitatory postsynaptic potential (fEPSP) required to elicit a half-maximal population spike (PS) amplitude was significantly larger in subchronic and chronic adolescent morphine exposure compared to the saline group. Therefore, subchronic and chronic adolescent morphine exposure altered synaptic transmission and plasticity in addition to learning and memory. Long-term morphine exposure during adolescence can interfere with neurodevelopment, making a persistent impression on plasticity and cognitive capability in adulthood.
青春期是神经发育的关键时期，在此期间接触阿片类药物会产生持久的神经和行为后果，并影响成年后的认知功能。本研究调查了青春期吗啡暴露对背侧海马体CA1区空间学习记忆和突触可塑性的影响。青春期Wistar大鼠接受递增剂量的吗啡，持续1天、5天和10天。急性吗啡组注射2.5mg/kg吗啡1天，亚慢性吗啡组注射5天，剂量从2.5mg/kg递增至12.5mg/kg，慢性吗啡组注射10天，剂量从2.5mg/kg递增至25mg/kg。在25天后大鼠成年时，通过莫里斯水迷宫（MWM）试验评估空间学习和记忆。此外，我们通过体外场电位记录测试成年大鼠背侧海马体可塑性的电生理特性。亚慢性和慢性青春期吗啡暴露损害了MWM试验中的空间学习和记忆。慢性吗啡组的基线突触反应增强，亚慢性和慢性吗啡组CA1区的长时程增强（LTP）受损。在成年期，与生理盐水组相比，亚慢性和慢性青春期吗啡暴露组诱发半数最大群体峰电位（PS）振幅所需的场兴奋性突触后电位（fEPSP）斜率显著更大。因此，亚慢性和慢性青春期吗啡暴露除了影响学习和记忆外，还改变了突触传递和可塑性。青春期长期接触吗啡会干扰神经发育，对成年期的可塑性和认知能力产生持久影响。
