Department of Health Sciences (DSS), Section of Clinical Pharmacology and Oncology, University of Florence, 50139 Florence, Italy.
Department of Physiotherapy, Center of Biological Sciences and Health, Federal University of Sao Carlos, São Carlos-SP 13565-905, Brazil.
Biomolecules. 2021 Apr 9;11(4):555. doi: 10.3390/biom11040555.
The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically ( mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the HR agonist (VUF16839) impaired both STM and LTM. HR agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the HR with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after HR stimulation are probably related to their function as heteroreceptors on cholinergic neurons.
识别熟悉同种个体的能力对于许多形式的社交互动至关重要，包括繁殖、建立优势等级和形成单配制物种的伴侣关系。许多激素和神经递质被认为在社交辨别中发挥关键作用。在这里，我们证明了组胺能神经传递的破坏或增强会对短期（STM）和长期（LTM）社交识别记忆产生不同的影响。无论是在慢性（缺乏组氨酸脱羧酶的小鼠）还是急性（用不可逆的 HDC 抑制剂 α-氟甲基组氨酸处理的小鼠）剥夺组胺的动物中，都观察到 LTM 受损，但 STM 没有受损。相反，通过刺激 HR 激动剂（VUF16839）限制组胺释放会损害 STM 和 LTM。用乙酰胆碱酯酶抑制剂多奈哌齐预处理可预防 HR 激动剂诱导的健忘症效应。用西普罗昔芬阻断 HR，进而增强组胺释放，会产生认知促进作用。根据这一假设，在 和 αFMH 处理的小鼠中，西普罗昔芬的认知促进作用均不存在。我们的研究结果表明，大脑组胺对于社交识别测试中的 LTM 巩固是必不可少的，但对于 STM 则不是。HR 刺激后观察到的 STM 损伤可能与其作为胆碱能神经元上的异源受体的功能有关。
