Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinepherine release in the hypothalamic paraventricular nucleus

Postnatal rearing conditions influence the development of hypothalamic-pitu itary-adrenal (HPA) responses to stress in the rat. Thus, postnatal handlin g dampens HPA responsivity to stress, while prolonged periods of maternal s eparation have the opposite effect. HPA responses to stress are initiated b y the release of corticotropin-releasing factor and/or arginine vasopressin from the neurones of the paraventricular nucleus of the hypothalamus (PVNh ). A major source of input to the PVNh arises from brainstem noradrenergic neurones with signalling occurring via alpha(1) adrenoreceptors. We examine d the noradrenergic response to stress in the PVNh in adult animals exposed to daily periods of handling or maternal separation over the first 2 weeks of life using microdialysis in conscious animals. Maternal separation incr eased, while handling greatly decreased and norepinepherine responses to re straint stress in the PVNh as compared to non-handled controls; the same pa ttern was observed for plasma adrenocorticotropic hormone (ACTH) responses to stress. Rearing condition did not affect either alpha(1) or alpha(2) rec eptor levels in the PVNh. However, alpha(2) receptor binding levels in the noradrenergic cell body regions of the locus coeruleus and the n. tractus s olitarius were significantly increased in handled animals. These alpha(2) r eceptors are principally located on noradrenergic neurones (i.e. autorecept ors) and inhibit noradrenaline release at terminal sites. The effects on al pha(2) receptor levels could serve as a mechanism for the differences in st ress-induced noradrenaline levels in the PVNh and in HPA activity among han dled vs non-handled and maternal separation animals. Thus, early life event s may serve to influence the differentiation of noradrenergic neurones and thus alter HPA responses stress in adulthood.