Cariprazine (Car) is a recently approved second generation antipsychotic (SGA) with
unique pharmacodynamic profile, being a partial agonist at both dopamine D-2/3 receptor
subtypes, with almost 10 times greater affinity towards D-3. SGAs are known to increase
body weight, alter serum lipids, and stimulate adipogenesis but so far, limited information
about the adverse effects is available with this drug. In order to study this new
SGA with such a unique mechanism of action, we compared Car to substances that are
considered references and are well characterized: olanzapine (Ola) and aripiprazole
(Ari). We studied the effects on body weight and also assessed the adipogenesis in
rats. The drugs were self-administered in two different doses to female, adult, Wistar
rats for six weeks. Weekly body weight change, vacuole size of adipocytes, Sterol
Regulatory Element Binding Protein-1 (SREBP-1) and Uncoupling Protein-1 (UCP-1) expression
were measured from the visceral adipose tissue (AT). The adipocyte's vacuole size,
and UCP-1 expression were increased while body weight gain was diminished by Car.
by increasing UCP-1 might stimulate the thermogenesis, that could potentially explain
the weight gain lowering effect through enhanced lipolysis.
