Behavioral consequences of methyllycaconitine in mice: a model of α7 nicotinic acetylcholine receptor deficiency

Add time:07/28/2019    Source:sciencedirect.com

Diminished expression of the α7 nicotinic acetylcholine receptor occurs in selected brain regions of patients with schizophrenia, which may account for pathophysiological abnormalities and some of the deficits in attention and information processing. In view of this neurotransmitter receptor deficit, we wished to characterize the behavioral consequences associated with the administration of methyllycaconitine (MLA), a competitive α7 nicotinic acetylcholine receptor antagonist, in mice. In this study, we injected groups of 12 outbred NIH Swiss male mice intraperitoneally with MLA (1.0, 3.2 and 10.0 mg/kg) and its saline vehicle. Thereafter, individual mice were observed over a one-hour interval and the intensity of a variety of behaviors were rated on a 4-point scale. The observed behaviors included: gnawing/chewing, rearing, grooming, sniffing, climbing, Straub tail, locomotion and ataxia. MLA produced statistically significant changes in the following observed behaviors: rearing, sniffing, climbing, and locomotion. A profile of the behavioral changes related to MLA administration in mice could lead to the development of a screening paradigm for α7 nicotinic acetylcholine receptor agonist interventions. Ideally, an effective α7 nicotinic acetylcholine receptor agonist intervention would target domains of psychopathology, especially cognitive symptoms that contribute to the profound functional disability that is often associated with schizophrenia.

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