Involvement of decreased muscarinic receptor function in prepulse inhibition deficits in mice reared in social isolation.

K Koda, Y Ago, K Yano, M Nishimura, H Kobayashi, A Fukada, K Takuma, T Matsuda

Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka, Suita, Osaka, Japan.

British journal of pharmacology 2011 Feb

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We have previously reported that galantamine, a weak acetylcholinesterase inhibitor, improves prepulse inhibition (PPI) deficits in mice reared in social isolation. ACh receptors are involved in the underlying mechanism of PPI, but whether rearing in social isolation causes dysfunction of the cholinergic system is unknown. In this study, we examined the involvement of muscarinic receptors in the improvement of PPI deficits induced by galantamine, and whether the cholinergic system is altered in mice reared in isolation. Three-week-old male ddY mice were housed in isolated cages for 6 weeks before the initiation of experiments to create PPI deficits. Cholinergic functions were determined by measuring the behavioural and neurochemical responses to nicotinic and muscarinic receptor agonists. The improvement by galantamine of social isolation-induced PPI deficits was blocked by scopolamine, a non-selective muscarinic antagonist, and telenzepine, a preferential M₁ receptor antagonist. Activation of M₁ receptors improved social isolation-induced PPI deficits. Social isolation did not affect choline acetyltransferase and acetylcholinesterase activities in the prefrontal cortex and hippocampus, but it reduced the locomotor-suppressive response to muscarinic agonist oxotremorine, but not to nicotine. The isolation also attenuated the M₁ receptor agonist N-desmethylclozapine-induced increase in prefrontal dopamine release. Galantamine improves PPI deficits of mice reared in social isolation via activation of M₁ receptors. Social isolation reduces the muscarinic, especially M₁, receptor function and this is involved in PPI deficits. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Citation

K Koda, Y Ago, K Yano, M Nishimura, H Kobayashi, A Fukada, K Takuma, T Matsuda. Involvement of decreased muscarinic receptor function in prepulse inhibition deficits in mice reared in social isolation. British journal of pharmacology. 2011 Feb;162(3):763-72