Research reportEffects of gonadectomy and serotonin depletion on inter-individual differences in anxiety-like behaviour in male Wistar rats

- Male rats were classified as “anxious” or non-“anxious” based on plus-maze performance.
- Gonadectomy eliminated this difference by enhancing “anxiety” in non-“anxious” rats.
- This effect of gonadectomy was reversed by inhibition of serotonin synthesis.
- TPH2 mRNA levels associated positively with “anxiety” only in intact rats.
- Serotonin appears to mediate an “anxiolytic” influence of androgens in male rats.

Previous studies in Wistar rats suggest inter-individual differences in anxiety-like behaviour as assessed using the elevated plus maze (EPM), both between sexes and among males, to be abolished by serotonin depletion. To shed further light on the influence of sex steroids and serotonin - and on the interplay between the two - on proneness for EPM-assessed anxiety in males, outbred Wistar rats were divided into those with high and low anxiety, respectively, and exposed to gonadectomy or sham operation followed by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine, or saline. Whereas gonadectomy enhanced anxiety-like behaviour in low anxiety rats so that these no longer differed in this regard from the high anxiety group, serotonin depletion reversed this effect, and also reduced anxiety in the low anxiety group regardless of gonadal state. A previously observed association between high anxiety-like behaviour and high expression of the serotonin-synthesizing enzyme tryptophan hydroxylase 2 (Tph2) in the raphe was confirmed in sham-operated animals but absent in gonadectomised rats, an ANCOVA revealing a significant interactive effect of baseline anxiety and gonadal state on Tph2 expression. It is suggested that androgens may contribute to upholding inter-individual differences in anxiety-like behaviour in male rats by interacting with serotonergic neurotransmission.