T178. MICROPIPETTE-GUIDED DRUG ADMINISTRATION (MDA) METHOD AS A NOVEL PHARMACOLOGICAL TREATMENT METHOD IN MICE: PRECLINICAL VALIDATION USING RISPERIDONE IN THE MATERNAL IMMUNE ACTIVATION MODEL OF NEURODEVELOPMENTAL DISORDERS

BACKGROUND: Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways how acute or chronic pharmacological treatments can be implemented, with each method having certain advantages and drawbacks. To overcome the main disadvantages of conventional administration routes, we implemented and validated a novel treatment method in mice, which we refer to as the Micropipette-guided drug administration (MDA) method. METHODS: The MDA administration method is based on using sweetened condensed milk solution as vehicle for pharmacological substances, which motivates the animals to consume vehicle and/or drug solutions voluntarily in the presence of the experimenter. First, we measured the corticosterone and pharmacokinetic changes after the administration of a vehicle or drug (Risperidone) solution via traditional oral gavage or by MDA. We then conducted a chronic treatment paradigm in the maternal immune activation model (MIA). Offspring treatment with risperidone started on post-natal day 70 and lasted for a total of 6 weeks, with behavioral testing occurring during the last two weeks of the treatment window. RESULTS: In a proof-of-concept study, we show that the pharmacokinetic profiles of the atypical antipsychotic drug, risperidone, are similar when administered via the MDA procedure or via the conventional oral gavage method. Unlike the latter, however, MDA did not induce the stress hormone, corticosterone. Furthermore, we assessed the suitability and validity of the MDA method in a mouse model of maternal immune activation, which is frequently used as a model of immune-mediated neurodevelopmental disorders. Using this model, we found that chronic treatment (> 4 weeks, once per day) with risperidone via MDA led to a dose-dependent mitigation of MIA-induced social interaction deficits and amphetamine hypersensitivity. DISCUSSION: Taken together, the MDA procedure described represents a novel pharmacological administration method for per os treatments in mice, which is easy to implement, cost effective, non-invasive, and less stressful for the animals than conventional oral gavage methods. Moreover, it allows for a more consistent and continual control of the dosages administered to the animals compared to methods involving the dissolution of a substance in the drinking water or contained within the food of the animals.