Sex differences in passive avoidance depend on the integrity of the central serotonergic system

Effects of the neurotoxin para-chloroamphetamine (PCA) on sex differences in passive avoidance were studied. Seven days prior to passive avoidance training and testing, male and female rats were injected with PCA (5 mg/kg) or physiological saline (SAL). Treatment effects on brain monoamines levels were evaluated in brains collected shortly after the passive avoidance test. Compared to SAL-treated control groups PCA severely reduced both serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) in the frontal cortex of males and females. Levels of dopamine (DA) and homovanillic acid (HVA) in the frontal cortex were not affected. These data are indicative of a strong and selective depression of the central 5-HT activity. PCA- and SAL-treated male and female rats were trained and tested in a two-compartment step-through passive avoidance apparatus. Sex differences in passive avoidance were clearly observed in the SAL-treated control groups; a higher number of males did not enter either compartment within the maximum test duration. After PCA treatment sex differences in passive avoidance were abolished, mainly resulting from an increase in the number of PCA-males reentering. Irrespective of sex or treatment subjects seldom failed to choose the nonshock compartment when entering during the passive avoidance test, indicating that disturbance of memory or learning cannot explain for the present results. Rather, the data are discussed in terms of a sex-specific role of central 5-HT in punishment-induced behavioral suppression.