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We provide the first evidence that prolactin is a neuromodulator of behavioral and neuroendocrine stress coping in the rat. In virgin female and male rats, intracerebral infusion of ovine prolactin (oPRL) into the lateral cerebral ventricle (intracerebroventricular) exerted an anxiolytic effect on the elevated plusmaze in a dose-dependent manner (0.1 and 1.0 g/5 l; p Ͻ 0.01). In contrast, downregulation of the expression of the long form of brain prolactin receptors by chronic intracerebroventricular infusion of an antisense oligodeoxynucleotide (ODN) (osmotic minipump, 0.5 g ⅐ 0.5 l Ϫ1 ⅐ hr Ϫ1 ; 5 d) increased anxiety-related behavior on the plus-maze compared with mixed bases-treated and vehicle-treated rats ( p Ͻ 0.01), again demonstrating an anxiolytic effect of PRL acting at brain level. Furthermore, in jugular vein-catheterized female rats, the stress-induced increase of corticotropin secretion was decreased after chronic intracerebroventricular infusion of oPRL (osmotic minipump, 1.0 g ⅐ 0.5 l Ϫ1 ⅐ hr Ϫ1 ; p Ͻ 0.05) and, in contrast, was further elevated by antisense targeting of the brain prolactin receptors ( p Ͻ 0.01). This provides evidence for a receptor-mediated attenuation of the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis by prolactin. The antisense ODN sequence was selected on the basis of secondary structure molecular modeling of the target mRNA to improve antisense ODN-mRNA hybridization. Receptor autoradiography confirmed the expected improvement in the efficacy of downregulation of prolactin receptor expression [empirically designed antisense, 30%; p Ͼ 0.05, not significant; adjustment of target position after mRNA modeling, 72%; p Ͻ 0.05). Taken together, prolactin acting at brain level has to be considered as a novel regulator of both emotionality and HPA axis reactivity.

Prolactin (PRL) has recently been shown to exert an anxiolytic effect in male and virgin female rats, as well as an inhibitory tone on hypothalamic-pituitary-adrenal (HPA) axis activity. Reduced emotional and neuroendocrine stress responses have been described in lactation, a time of high blood PRL levels. Here we tested brain PRL-receptor (PRL-R)-mediated effects on anxiety, maternal behaviour, HPA axis and oxytocin stress responses in lactating rats. Chronic intracerebroventricular (i.c.v.) infusion of antisense oligonucleotides against the long form of the PRL-R (AS; osmotic minipump, 0.5 microg/0.5 microL/h) in order to downregulate brain PRL-R expression increased the anxiety-related behaviour on the elevated plus maze (P < 0.01) compared with mixed bases- and vehicle-treated rats. Also, PRL-R AS treatment impaired maternal behaviour (P < 0.05), whereas physiological parameters of lactation (weight gain of the litter, number of milk ejection reflexes during a 20-min suckling period) were not affected. PRL-R AS treatment further evoked an increase (P < 0.05) in the stress-induced adrenocorticotropin release, demonstrating an inhibitory role of PRL on HPA axis responses in lactation. Inhibition of stress responses of the oxytocin system by brain PRL was evidenced by higher stress-induced (P < 0.05) plasma oxytocin concentration in PRL-R AS-treated lactating rats and, in contrast, decreased stress-induced oxytocin release (P < 0.01) in chronic i.c.v. ovine PRL-treated (1 microg/0.5 microL/h) virgin rats. Finally, an increased expression of the hypothalamic PRL gene was seen by RT-PCR in pregnancy and lactation, suggesting an activated state of the brain PRL system during the peripartum period. In summary, activation of the brain PRL system in the peripartum period significantly contributes to emotional and neuroendocrine adaptations, including downregulation of the responsiveness of the HPA axis and oxytocin systems to stressors seen at this time.

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The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project.Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders.