Development of a mouse model of haloperidol-induced vacuous chewing movements

TRIBBIA LT.; BELFORTE JE.; GERSHANIK OS.; MURER MG.; TARAVINI IRE.

Congreso; XXXVI Congreso Anual (VIRTUAL) de la Sociedad Argentina de Investigación en Neurociencia.; 2021

Sociedad Argentina de Investigación en Neurociencia

The development of tardive dyskinesias (TD) is frequently associated with chronic antipsychotic treatment in schizophrenic patients. These movement disorders have a high prevalence, reaching approximately 60%. TD can persist even after many years of discontinuation of the drug that triggered them, and become an irreversible phenomenon. There is no effective treatment that allows an acceptable solution to the problem, so it is important to advance in an adequate knowledge of the alterations that underlie its appearance to minimize the deterioration in the quality of life of patients. To study whether the development of TD induced by chronic treatment with haloperidol correlates with a modification of striatal synaptic connectivity, we have developed a model of vacuous chewing movements (VCM) in mice. Wild-type mice received a daily dose of 1.5 mg/kg ofhaloperidol for 30 days, then the dose was increased to 2 mg/kg for a further 30 days and behavior was observed every 5 days. After 60 days, the treatment was discontinued and the behavior was observed for a further 30 days. Orofacial movements were recorded: protrusion of the tongue, wide-range chewing movements, subtle chewing movements, and jaw tremors. Anxiety-like behavior was also assessed with the open field test and the light-dark test. With this haloperidol administration protocol we were able to induce the development of VCM of great intensity that lasted even after the pharmacological treatment was discontinued.