Antipsychotic drugs (APDs) have a variety of important therapeutic applications for neuropsychiatric disorders. However, they are routinely prescribed off-label across all age categories, a controversial practice given their potential for producing metabolic and extrapyramidal side effects. Evidence also suggests that chronic treatment with some APDs may lead to impairments in cognition and decreases in brain volume, although these findings are controversial. The purpose of the studies described here was to evaluate one of the most commonly prescribed APDs, quetiapine, for chronic effects on recognition memory, brain-derived neurotrophic factor (BDNF), its precursor proBDNF, as well as relevant downstream signaling molecules that are known to influence neuronal plasticity and cognition. Multiple cohorts of adult rats were treated with quetiapine (25.0 mg/kg/day) for 30 or 90 days in their drinking water then evaluated for drug effects on motor function in a catalepsy assessment, recognition memory in a spontaneous novel object recognition (NOR) task, and BDNF-related signaling molecules in the post mortem hippocampus via Western Blot. The results indicated that oral quetiapine at a dose that did not induce catalepsy, led to time-dependent impairments in NOR performance, increases in the proBDNF/BDNF ratio, and decreases in Akt and CREB phosphorylation in the hippocampus. These results indicate that chronic treatment with quetiapine has the potential to adversely affect recognition memory and neurotrophin-related signaling molecules that support synaptic plasticity and cognitive function. Given the widespread use this APD across multiple conditions and patient populations, such long-term effects observed in animals should be considered.

抗精神病药物（APD）对于神经精神疾病具有多种重要的治疗应用。然而，所有年龄段的患者通常都会在标签外开处方，考虑到它们可能产生代谢和锥体外系副作用，这是一种有争议的做法。还有证据表明，某些 APD 的长期治疗可能会导致认知障碍和脑容量减少，尽管这些发现存在争议。本文所述研究的目的是评估最常用的 APD 之一喹硫平对识别记忆、脑源性神经营养因子 (BDNF)、其前体 proBDNF 以及已知的相关下游信号分子的慢性影响影响神经元的可塑性和认知。多组成年大鼠在饮用水中接受喹硫平（25.0 毫克/公斤/天）治疗 30 或 90 天，然后评估药物对僵直评估中运动功能的影响，以及自发新物体识别 (NOR) 中对识别记忆的影响通过蛋白质印迹分析死后海马中的 BDNF 相关信号分子。结果表明，口服喹硫平的剂量不会引起强直性昏厥，会导致 NOR 功能出现时间依赖性损伤、proBDNF/BDNF 比率增加以及海马 Akt 和 CREB ​​磷酸化降低。这些结果表明，长期使用喹硫平治疗可能会对识别记忆和支持突触可塑性和认知功能的神经营养蛋白相关信号分子产生不利影响。鉴于这种 APD 在多种疾病和患者群体中的广泛使用，应考虑在动物中观察到的这种长期影响。