Progesterone reduces hyperactivity of female and male dopamine transporter knockout mice

There are gender differences in prevalence, course, and/or prognosis of schizophrenia. Yet, neurobiological factors that may account for the more favorable outcomes of women with schizophrenia are not well understood. Evidence that the steroid hormone, progesterone (P4), may influence mood and/or arousal among some people with schizophrenia led us to examine the effects of P4 on dopamine transporter knockout (DATKO) mice, an animal model of schizophrenia. Our hypothesis was that P4 would have greater effects than vehicle to improve the behavioral phenotype of DATKO, more so than wildtype, mice. Young adult, male and female DATKO mice and their wildtype counterparts were subcutaneously administered P4 (10 mg/kg) or vehicle 1 h prior to testing in pre-pulse inhibition (PPI), activity monitor, or open field. DATKO mice had impaired PPI compared to their wildtype counterparts, but there was no effect of P4. In the activity monitor, DATKO mice showed significantly greater distance traveled during the 60 min test compared to wildtype controls. In the open field, DATKO mice made a significantly greater number of total, but fewer central, entries than did wildtype mice. Administration of P4 decreased the hyperactivity of DATKO mice in the activity monitor and open field, but did not alter motor behavior of wildtype mice. P4 increased the number of central entries made by DATKO and wildtype mice. Thus, P4 administration to DATKO female or male mice partially attenuated their hyperactive phenotype.