Immature serotonergic regulation of anxiety‐like behavior in adolescent male rats

Abstract

Novelty seeking and risk taking peak during adolescence. The goal of this study was to investigate whether immature serotonergic function contributes to adolescent risk taking using the light/dark (LD) test as a model of rodent behavior in an aversive environment.Adult (PN67–70) and adolescent (PN28–32) male rats were given a single dose of fluoxetine (10 mg/kg), the 5‐HT1A agonist 8‐hydroxy‐2‐(dipropylamino)tetralin (8‐OH DPAT, 0.25 or 0.5 mg/kg), the 5‐HT2 agonist meta‐chlorophenylpiperazine (mCPP, 0.5 or 1 mg/kg), or vehicle and placed in the LD box. The latency to emerge into the light and time in the light compartment were measured for 15 minutes. The effects of fluoxetine (2.5, 5, and 10 mg/kg i.p.) on extracellular serotonin in the medial prefrontal cortex (mPFC) were measured by microdialysis followed by HPLC. Adolescents were less sensitive to the anxiogenic effects of fluoxetine and 8‐OH DPAT, but not mCPP. There was no age difference in the increase in mPFC serotonin after fluoxetine. Adolescents treated with 8‐OH DPAT exhibited reduced activation of the central amygdala and paraventricular hypothalamus, as shown by c‐Fos immunostaining.These data show that serotonergic induction of behavioral inhibition in the LD test is deficient in adolescent rats. This may be due to immature 5‐HT1A receptor modulation of the neural circuits mediating LD behavior.Supported by DA019114 and F31DA032532