A regional study of sex differences in rat brain serotonin

1. Male and female rats were compared with respect to serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) levels in five brain regions (brainstem, hypothalamus/preoptic area, corpora striata, limbic forebrain and cortex). Brain 5-HT synthesis rate was also studied in the two sexes. 2. There were no consistent gender differences in the dopaminergic system. 3. In contrast, the serotonergic system was more expressed in females: 5-HT levels were significantly higher in females than in males in the brainstem and limbic forebrain and tended to be so in the cortex. 5-HIAA levels were significantly higher in females in all five brain regions. The 5-HIAA/5-HT ratios were significantly higher in females in the hypothalamus/preoptic area and limbic forebrain and tended to be so in the striatum and cortex. Tryptophan concentrations were significantly higher in females in the brainstem, striatum and cortex. In no brain region were 5-HT, 5-HIAA or tryptophan levels higher in males. Following L-amino acid decarboxylase inhibition 5-hydroxytryptophan (5-HTP) accumulation was more pronounced in the female rat brain. 4. Taken together these results suggest that the brain 5-HT system has a higher potential in female than in male rats. This sex difference is not restricted to a specific region but seems to exist generally in the brain.