BACKGROUND: The neuropeptide cholecystokinin (CCK) has been implicated in the neurobiology of anxiety and panic disorders, as well as in dopamine-related behaviours. Anxiety and panic-disorders are twice as common in females compared to males, but studies of females are rare, although increasing in number. Limited studies have found that CCK fluctuates in limbic regions during the estrous cycle, and that CCK and its receptors are sensitive to estrogen.

AIM/PURPOSE: The aim of the present work was to study the acute effects of 17β-estradiol on anxiety-like behaviour and on CCK-like immunoreactivity (LI) in the female rat brain (amygdala, hippocampus, nucleus accumbens, and cingulate cortex).

METHODS: Four groups of female Sprague-Dawley rats were used: ovariectomized, ovariectomized+17β-estradiol-replacement, sham, and sham+17β-estradiol-replacement. The effect of 17β-estradiol-replacement on anxiety-related behaviour was measured in all animals on the elevated plus maze 2-24h after injection. CCK-LI concentration was measured in punch biopsies by means of radioimmunoassay.

RESULTS: 17β-estradiol decreased anxiety-like behaviour 2h after administration in ovariectomized and sham-operated animals, as demonstrated by increased exploration of the open arms compared to respective sesame oil-treated controls. This effect was not present when testing occurred 24h post-treatment. The rapid behavioural effect of 17β-estradiol was accompanied by changes in CCK-LI concentrations in regions of the limbic system including cingulate cortex, hippocampus, amygdala and nucleus accumbens.

CONCLUSION: Although the interpretation of these data requires caution since the data were collected from two different experiments, our results suggest that estrogen-induced anxiolytic effects may be associated with changes of the CCK-system in brain regions controlling anxiety-like behaviour.