Amphetamine treatment affects the extra-hypothalamic vasopressinergic system in a sex- and nucleus-dependent manner.

The lateral septum (LS), a brain structure implicated in addictive behaviours, regulates the activation of dopaminergic neurones in the ventral tegmental area. Vasopressinergic projections from the extended amygdala to the LS, which are sexually dimorphic, could be responsible for the vulnerability to addiction in a sex-dependent manner. The present study aimed to investigate the modulatory effects of amphetamine (AMPH) on the expression of vasopressin (AVP) in the vasopressinergic extra-hypothalamic system in sensitised male and female rats. Adult male and female Sprague-Dawley rats underwent an AMPH-locomotor sensitisation protocol. Acute AMPH increased AVP mRNA expression in the medial amygdala (MeA), whereas AMPH-induced sensitisation increased AVP mRNA expression in the bed nucleus of the stria terminalis (BNST) only in females. Interestingly, the increase in AVP expression in BNST was higher in oestrus females compared to dioestrus females and acute AMPH resulted in a decrease in AVP levels in the LS, only in males. Thus, there are complex and region-specific interactions between AMPH and the extra-hypothalamic vasopressinergic system in the brain, underlying possible alterations in different behaviours caused by acute and chronic AMPH exposure.

Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 µl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 µl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter.

Gender-dependent effects of early maternal separation and variable chronic stress on vasopressinergic activity and glucocorticoid receptor expression in adult rats.

The aim of the present study was to investigate the influence of early maternal separation on Fos, arginine vasopressin (AVP) and glucocorticoid receptor (GR) expression in the medial parvocellular portion of the paraventricular hypothalamic nucleus (PaMP), and GR expression in the hippocampus of adult male and female rats subjected to variable chronic stress (VCS). Male and female Wistar rats were isolated 4.5 h daily, during the first 3 weeks of life. At 48 days of age, the rats were exposed to VCS. Nonmaternally separated (NMS) females had a higher number of activated AVP neurons than NMS male rats. Maternally separated (MS) females subjected to VCS also showed a higher number of Fos/AVP double-labeled neurons than males with the same treatment. Males and females subjected to early maternal separation and VCS, compared with the MS animals, showed a decrease in the expression of GR in the PaMP. As regards GR expression in the hippocampus, MS animals subjected to VCS as adults, both males and females, showed an increase in GR expression in the subfields CA1, CA2 and CA3. The increase in AVP-immunoreactive neurons coexpressing Fos in response to stress in females exposed to early maternal separation suggests that perhaps early life stress results in a more reactive neuroendocrine stress response in females. Furthermore, our results demonstrate that the different anatomical levels of the hypothalamic-pituitary-adrenal axis have different roles related to its stress response and support the evidence of regional specificity in GR regulation.

Sex differences in rats: effects of chronic stress on sympathetic system and anxiety.

In this study we tested whether periodic maternal deprivation (MD) (4.5 h daily during the first 3 weeks of life) caused chronic changes in anxiety and medullo-adrenal responses to chronic stress in either male or female adult (2.5 months of age) rats, or both. Repeated maternal deprivation had a sex-specific effect on epinephrine (E) and norepinephrine (NE) levels: an increase in both measures was observed only in females. Unpredictable stress did not produce changes on plasma catecholamine levels either in males or females. However, when the females were maternally deprived as well as stressed they showed an increase in plasma NE p < 0.05. On the other hand, non-maternally deprived (NMD), maternally-deprived and stressed males showed high levels of catecholamines compared to females p < 0.001. In the elevated plus maze test, MD-treated males displayed a slight increase in anxiety-related behavior compared with NMD rats. This was indicated by a reduction in the time spent on the open arms, whereas females showed less anxiety, indicated by an increase in the number of entries, and in the time spent on the open arms. After exposure to chronic stress only the females displayed decreased anxiety-related behavior. These results suggest that there are sex-induced effects in emotional reactivity, perception of the stressor and in the evaluation of novel situations. Thus, maternal deprivation and chronic variable stress caused both long-term alterations in sympathetic response and gender-dependent changes in the anxiety index of adult rats.