Thursday Abstracts

Abstract

Background: Schizophrenics display several phenotypic changes, including sleep disturbance, some of which are believed to be associated with aberrant dopamine transmission. We examined circadian and open field behavior (OFB) in mice carrying a truncation in the Disc1 gene (a risk factor for schizophrenia) with and without chronic Levodopa treatment at younger and older adult ages in order to determine whether Disc1 truncation and Levodopa treatment alter these behaviors. Methods: Circadian wheel-running activity was monitored in one cohort of male and female mice at post-natal day 110 (P110) in a 12:12 Light:Dark photoperiod (LD) and in constant dark (DD). At P175 phase response to a light pulse at circadian time 15 hours was measured. LD and DD assays were repeated at P232. A second cohort of mice, all male, was implanted with timedrelease Levodopa capsules at P60. Open field behavior was observed at P70 for 7 minutes, followed by circadian rhythm assays and OFB re-testing at P113. Total square entries (TSE) for OFB estimated overall activity, whereas central square entries (CSE) estimated anxiety. Results: Cohort one demonstrated significant sex differences for most circadian variables, but no Disc1 effect or Disc1 by sex interaction. Cohort two showed no treatment effects of Disc1 and Levodopa for circadian measures or OFB at P70, but at P113 a significant Levodopa by Disc1 interaction occurred for TSE and CSE. As CSE = TSE-PSE (peripheral square entries), these results indicate that the effect observed in TSE is driven by that in CSE. Conclusions: These findings suggest that increased dopamine metabolism and Disc1 truncation do not alter circadian behavior, but may affect adult neuroplasticity in a manner that alters anxiety behavior only in older stages of adulthood.