Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Department of Anatomy, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
Psychopharmacology (Berl). 2021 Aug;238(8):2225-2234. doi: 10.1007/s00213-021-05847-2. Epub 2021 Apr 23.
Episodic memory retrieval is fundamental for daily activities of humans and animals. Muscarinic cholinergic signaling is important for memory functioning and shows gender-dependent response in episodic memory retrieval. Dopamine D2 receptors influence memory formation and retrieval by influencing cholinergic signaling in the brain. This study aimed to determine the gender-dependent effects of D2 and muscarinic activity on memory retrieval. Male and female mice were trained for Morris water maze test and contextual fear conditioning. Memory retrieval was assessed following sub-chronic treatment (for 5 days) with D2 antagonist (risperidone 2.5 mg/kg) alone or in combination with scopolamine (1 mg/kg) or donepezil (1 mg/kg). Open field test was performed prior to the retrieval test to evaluate effects of risperidone treatment on locomotor activity and exploratory behavior. Risperidone co-treatment with donepezil impaired spatial memory retrieval in males only. Muscarinic and D2 simultaneous antagonism tend to impair fear retrieval in males but significantly enhanced retrieval of fear memories in female mice. These results suggest that D2 signaling influence muscarinic receptor activity during memory retrieval in gender-dependent manner.
情景记忆检索对于人类和动物的日常活动至关重要。毒蕈碱型乙酰胆碱能信号对于记忆功能很重要,并且在情景记忆检索中表现出性别依赖性反应。多巴胺 D2 受体通过影响大脑中的胆碱能信号来影响记忆的形成和检索。本研究旨在确定 D2 和毒蕈碱活性对记忆检索的性别依赖性影响。雄性和雌性小鼠接受 Morris 水迷宫测试和情境恐惧条件反射训练。在进行为期 5 天的慢性处理后(使用 2.5mg/kg 的利培酮),单独或与东莨菪碱(1mg/kg)或多奈哌齐(1mg/kg)联合处理后,评估记忆检索。在检索测试之前进行旷场测试,以评估利培酮处理对运动活动和探索行为的影响。利培酮与多奈哌齐联合治疗仅损害雄性动物的空间记忆检索。毒蕈碱和 D2 的同时拮抗作用可能会损害雄性动物的恐惧检索,但会显著增强雌性小鼠的恐惧记忆检索。这些结果表明,D2 信号在性别依赖性的方式下影响记忆检索过程中的毒蕈碱受体活性。