Histamine-inducing drugs improve long-term memory recall

The drugs helped mice and humans recall long-term object memories.

Featured in Asia Research News 2020 Magazine

Scientists have long been looking for a method to recall lost memories. Now, researchers have shown that drugs that induce histamine release in the brain can help mice and humans retrieve long-term object memories.

Histamine has many important functions in the body, including roles in learning and memory. Compounds that induce its release are therefore potential candidates for treating memory disorders. Scientists from Hokkaido University, in collaboration with colleagues at the University of Tokyo and Kyoto University, looked into a group of chemicals that induce histamine release from the brain’s nerve cells by binding to their histamine H3 receptor.

Normally, chemical compounds in the brain bind to the histamine H3 receptor to inhibit histamine synthesis and release by nerve cells. In contrast, a class of drugs, called histamine H3 receptor inverse agonists, can bind to the receptor and produce the opposite effect.

Hokkaido University pharmacologist Hiroshi Nomura and his team tested the effects of these agonists on long-term memory recall. Mice were shown two objects, one they had seen before in training and one that was new. Mice usually forget objects after three days. However, the mice were able to remember objects seen up to 28 days earlier 30 minutes after the researchers gave them an injection of one of two agonists: thioperamide or betahistine.

Next, human participants were asked to look at 128 images of familiar objects, like eyeglasses or a wristwatch. More than a week later, the participants were given betahistine oral capsules. After half an hour had passed, they were shown the images again, some they had seen earlier and some that were new.

Participants who had taken the drugs were better at remembering which images they had seen before compared to a group that were given a placebo. The drugs were more effective for items that are more difficult to remember and in participants with poorer memories. Further tests showed that histamine activates nerve cells in the perirhinal cortex region of the brain, which is important for processing sensory information and in a variety of memory functions.

The results highlight an important interaction between histamine signalling in the central nervous system and memory recall. Clarifying the role of histamine in memory could have implications for the treatment of long-term memory loss in conditions such as Alzheimer’s disease and other forms of dementia.


For further information, contact:
Assistant Professor Hiroshi Nomura 
Graduate School of Pharmaceutical Sciences
Hokkaido University
E-mail: [email protected]


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Published: 12 Jan 2020


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Nomura H. et al. Central histamine boosts perirhinal cortex activity and restores forgotten object memories Biological Psychiatry 86, 230–239 (2019).