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    Social isolation stress markedly reduces the response of cortical dopaminergic neurons to pleasurable stimuli

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    The mesocortical dopaminergic system is involved in the coping response to environmental stimuli. Accordingly, both stressful and pleasurable stimuli can induce an increase in the extracellular concentration of dopamine (DA) in the medial prefrontal cortex of rats. Social isolation (SI), a widely used animal model of depression, is able to induce anhedonia in rats, reducing the consume of sucrose. In our experiments we investigated, by vertical microdialysis, whether SI can modify the changes in DA extracellular concentration induced by anticipation and consumption of food in rats trained to consume their daily meal in two hours. In control, group housed (GH), rats DA extracellular concentration showed a marked increase (+180% over basal values) 80 min before food presentation, reached a maximum during food consumption (+350%), and returned to basal values when food was taken away. In SI rats the food restriction-induced increase in DA output was almost completely abolished with respect to GH animals, both in the anticipatory and consummatory phase. In order to restore the response of mesocortical DAergic neurons to food, we administered the antidepressant drug imipramine (IMI, 20 mg/kg/day for 21 days) in a chocolate (CH) pellet that was presented to the animals one hour before food. This way of administration was chosen to avoid to handle the animals as handling has been shown to abolish the effect of SI on several paradigms. Control animals received only the CH pellet. Our results showed that in SI rats neither CH or IMI administered in CH were able to restore the food-induced increase in DA extracellular concentration. In GH rats the anticipatory increase in DA output was shifted before CH presentation, while food consumption still induced an increase in DA output similar to that observed in control rats. IMI administered with CH was able to enhance the increase in DA output observed both in the anticipatory and consummatory phase. Our data confirm the crucial role of mesocortical dopaminergic neurons in the regulation of emotion and suggest that the alterations in mood state induced by SI are able to blunt the response of cortical dopaminergic neurons to pleasurable stimuli

    Social isolation blunted the response of mesocortical dopaminergic neurons to chronic ethanol voluntary intake

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    Previous studies have shown that stress can increase the response of mesolimbic dopaminergic neurons to acute administration of drugs of abuse included ethanol. In this study, we investigated the possible involvement of the mesocortical dopaminergic pathway in the development of ethanol abuse under stress conditions. To this aim we trained both socially isolated (SI) and group housed (GH) rats to self administer ethanol which was made available only 2 ha day (from 11:00 to 13:00 h). Rats have been trained for 3 weeks starting at postnatal day 35. After training, rats were surgically implanted with microdialysis probes under deep anesthesia, and 24 hlater extracellular dopamine concentrations were monitored in medial prefrontal cortex (mPFC) for the 2 hpreceding ethanol administration (anticipatory phase), during ethanol exposure (consummatory phase) and for 2 hafter ethanol removal. Results show that, in GH animals, dopamine extracellular concentration in the mPFC increased as early as 80 min before ethanol presentation (+50% over basal values) and remained elevated for 80 min during ethanol exposure. In SI rats, on the contrary, dopamine extracellular concentration did not show any significant change at any time point. Ethanol consumption was significantly higher in SI than in GH rats. Moreover, mesocortical dopaminergic neurons in SI animals also showed a decreased sensitivity to an acute administration of ethanol with respect to GH rats. Our results show that prolonged exposure to stress, as in social isolation, is able to induce significant changes in the response of mesocortical dopaminergic neurons to ethanol exposure and suggest that these changes might play an important role in the compulsivity observed in ethanol addictio

    Changes in stress-stimulated allopregnanolone levels induced by neonatal estradiol treatment are associated with enhanced dopamine release in adult female rats: reversal by progesterone administration

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    Background Allopregnanolone plays a role in the stress response and homeostasis. Alterations in the estrogen milieu during the perinatal period influence brain development in a manner that persists into adulthood. Accordingly, we showed that a single administration of estradiol benzoate (EB) on the day of birth decreases brain allopregnanolone concentrations in adult female rats. Objective We examined whether the persistent decrease in allopregnanolone concentrations, induced by neonatal EB treatment, might affect sensitivity to stress during adulthood. Methods Female rats were treated with 10 μg of EB or vehicle on the day of birth. During adulthood, the response to acute foot shock stress was assessed by measuring changes in brain allopregnanolone and corticosterone levels, aswell as extracellular dopamine output in the medial prefrontal cortex (mPFC). Results Neonatal EB treatment enhanced stress-stimulated allopregnanolone levels in the hypothalamus, as well as extracellular dopamine output in the mPFC; this latest effect is reverted by subchronic progesterone treatment. By contrast, neonatal EB treatment did not alter stress-induced corticosterone levels, sensitivity to hypothalamic-pituitary-adrenal (HPA) axis negative feedback, or abundance of glucocorticoid and mineralocorticoid receptors. Conclusions The persistent decrease in brain allopregnanolone concentrations, induced by neonatal EB treatment, enhances stress-stimulated allopregnanolone levels and extracellular dopamine output during adulthood. These effects are not associated to an impairment in HPA axis activity. Heightened sensitivity to stress is a risk factor for several neuropsychiatric disorders; these results suggest that exposure to estrogen during development may predispose individuals to such disorders

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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