Pharmacokinetic validation of a new protocol of chronic oral administration of aripiprazole in male C57 Bl/6 mice through drinking solution

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Schizophrenia is a chronic mental illness, with a prevalence of about 1%. The symptoms are classified in three categories: positive symptoms, negative symptoms and deficits in cognitive function. Regarding the pharmacological treatment, current antipsychotics mainly improve positive symptoms while negative and cognitive symptoms remain inadequately treated. Among them, aripiprazole, through its pharmacological properties results in regulation of positive symptoms and, to a lesser extent, to negative and cognitive ones. Drug treatment studies in animals typically employ administration methods such as injection or gavage, which is time-consuming over long periods, does not reflect route of administration used in patients, and cause substantial stress in animals. We assessed herein the pharmacokinetic properties and behavioural effects of aripiprazole after chronic administration via drinking solution in C57Bl/6 mice. Results show that subchronic administration of 1 and 10 mg/kg doses of aripiprazole via drinking solution present significant blood concentrations, without any significant effect on the spontaneous activity of mice (between 10 a.m. and 3 p.m.). Furthermore, we described for the first time to our knowledge the main pharmacokinetic parameters of aripiprazole after gavage acute administration (10 mg/kg). Collectively, all of these data will be very useful in future projects including chronic administrations (several months) of this antipsychotic. • Pharmacokinetic and behavioral validation of subchronic aripiprazole administration via drinking solution (DS) in mice. •DS subchronic administration of 1 and 10 mg/kg induce significative blood concentration during behavioral exploration period. •Residual blood concentration after DS were lower compared to oral gavage (OG) at equivalent doses. •Locomotor activity remained consistent for a same dose at the 3 times of behavioral study for DS administration.