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Effect of histamine on muscimol-induced working memory deficits in radial maze performance
Yasuko Yamamoto1, Azusa Mikami, Yoko Fujii
1Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Abstract:
We investigated the participation of gamma-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABA(A) agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observed with reference memory error. Donepezil and tacrine (cholinesterase inhibitors) antagonized the muscimol-induced spatial memory deficits. Histidine (1500 mg/kg, i.p.) also improved the total error and working memory error induced by muscimol. At this dose, histidine caused a significant increase in the histamine content of the cortex, hippocampus, and hypothalamus in rats. In addition, the intra-hippocampal injection of histamine also antagonized muscimol-induced spatial memory deficits. The practical conclusion is that the GABA(A) receptor of the medial septal area plays an important role in working memory, and also, the disturbance of working memory induced by muscimol is mediated not only by cholinergic but also by histaminergic systems in the spatial memory of rats.
Insights
Gamma-aminobutyric acid (GABA) neurons in the medial septum are crucial for working memory. Histamine and cholinesterase inhibitors can counteract memory deficits caused by GABAergic disruption.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- The medial septal area (MSA) plays a role in cognitive functions.
- Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter in the brain.
Purpose of the Study:
- To investigate the role of GABAergic neurons in the medial septal area (MSA) in spatial working memory using an eight-arm radial maze in rats.
- To explore the potential therapeutic effects of cholinesterase inhibitors and histidine on memory deficits induced by GABAergic system disruption.
Main Methods:
- Intra-septal injection of muscimol (a GABA(A) agonist) to impair MSA function.
- Performance assessment using the eight-arm radial maze to measure total errors, working memory errors, and reference memory errors.
- Administration of donepezil, tacrine (cholinesterase inhibitors), and histidine (i.p.) to evaluate their effects on muscimol-induced deficits.
- Measurement of histamine levels in brain regions (cortex, hippocampus, hypothalamus) after histidine administration.
- Intra-hippocampal injection of histamine to assess its direct effect on spatial memory.
Main Results:
- Muscimol injection into the MSA significantly increased total errors and working memory errors, but not reference memory errors.
- Donepezil and tacrine administration antagonized the muscimol-induced spatial memory deficits.
- Histidine administration (1500 mg/kg, i.p.) improved both total and working memory errors caused by muscimol.
- Histidine increased histamine levels in the cortex, hippocampus, and hypothalamus.
- Direct intra-hippocampal administration of histamine also counteracted the muscimol-induced spatial memory impairments.
Conclusions:
- GABA(A) receptors in the medial septal area are critical for spatial working memory.
- The working memory deficits induced by muscimol in the MSA are modulated by both cholinergic and histaminergic systems.
- Histamine, particularly in the hippocampus, may play a significant role in mitigating GABAergic system-disrupted spatial memory impairments.
