Altered development of the rat brain serotonergic system after disruptive neonatal experience

A single disruptive experience, a cold treatment, on postnatal day 1 elevated open-field activity and reduced reaction to handling in rats tested more than 240 days later. Neurochemical mechanisms underlying these behavioral phenomena were examined by monitoring the development of the rat brain serotonergic system. After cold treatment, elevations in 5-hydroxytryptamine levels of a preparation of forebrain plus midbrain could be first detected on postnatal day 16 in both sexes. A more detailed regional dissection of the brain showed that such increases occurred in the cerebrum, midbrain, septum-thalamus, and hypothalamus-preoptic area. Rats treated on postnatal days 1 or 6 showed increased 5-hydroxytryptamine levels, whereas animals treated on postnatal day 10 did not, a finding that points to a possible "critical period" of sensitivity. Results of adrenalectomy and corticosterone injections suggest that the influence of the adrenal gland cannot account for the elevation in brain serotonin. Furthermore, the gonadal steroids, estradiol and testosterone, alter brain 5-hydroxytryptamine independently of early experience, as distinguished by the time of appearance, periods of sensitivity, and the direction of monoamine changes. These findings are discussed in relation to the maturation of the neuroendocrine systems governing adrenal and gonadal function.