Effect of antidepressants and adolescent stress on catecholamine transmission in the rat bed nucleus of stria terminalis (BNST): a microdialysis study

Rationale: Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria terminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. Chronic stress, particularly at developmental stage, has long-lasting deleterious effects on several cortico-limbic areas. Abnormal catecholamine transmission in the BNST evoked by chronic stress exposition at peri-adolescent age may be interpreted as relevant neurochemical marker at the onset of adolescent or adult depression. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. Among new experimental strategies investigated for the theraphy of depression, the treatment with sub-anesthetic doses of ketamine has been suggested to be one of the most promising. Objectives: The aims of this study, carried out by means of in vivo microdialysis, were: (i) ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST; (ii) ascertain the acute effects that sub-anesthetic doses of ketamine have on dopamine and norepinephrine output in the BNST; (iii) ascertain whether peri-adolescent unpredictable chronic stress could produce changes in dopamine and norepinephrine transmission in the BNST. Results: We observed the following: (i) all the antidepressants tested (5-20 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (ii) ketamine (10-40 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (iii) peri-adolescent unpredictable chronic stress determined changes of basal and stimulated catecholamine output. Conclusions: These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants, and in the effects of stress. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders

Effect of antidepressants and adolescent stress on catecholamine transmission in the rat bed nucleus of stria terminalis (BNST): a microdialysis study

Rationale: Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria terminalis (BNST) is considered a relay station in mediating the activation of stress response but also in the acquisition and expression of emotions. Chronic stress, particularly at developmental stage, has long-lasting deleterious effects on several cortico-limbic areas. Abnormal catecholamine transmission in the BNST evoked by chronic stress exposition at peri-adolescent age may be interpreted as relevant neurochemical marker at the onset of adolescent or adult depression. BNST is richly innervated by monoamines and sends back projections to the nucleus of origin. We previously showed that the administration of selective blockers of norepinephrine transporter (NET) increases the extracellular concentration (output) of dopamine, suggesting that dopamine could be captured by NET in the BNST. Among new experimental strategies investigated for the theraphy of depression, the treatment with sub-anesthetic doses of ketamine has been suggested to be one of the most promising. Objectives: The aims of this study, carried out by means of in vivo microdialysis, were: (i) ascertain the acute effects that antidepressants with varying mechanisms of action have on dopamine and norepinephrine output in the BNST; (ii) ascertain the acute effects that sub-anesthetic doses of ketamine have on dopamine and norepinephrine output in the BNST; (iii) ascertain whether peri-adolescent unpredictable chronic stress could produce changes in dopamine and norepinephrine transmission in the BNST. Results: We observed the following: (i) all the antidepressants tested (5-20 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (ii) ketamine (10-40 mg/Kg i.p.) increased the output of catecholamines, dose dependently; (iii) peri-adolescent unpredictable chronic stress determined changes of basal and stimulated catecholamine output. Conclusions: These results suggest that catecholamine transmission in the BNST may be part of a common downstream pathway that is involved in the action mechanism of antidepressants, and in the effects of stress. Consequently, it is hypothesized that a dysfunction of neuronal transmission in this brain area may have a role in the etiology of affective disorders

Role of Prefrontal Cortex Dopamine and Noradrenaline Circuitry in Addiction

Understanding the mechanisms of drug dependence has been the goal of a large number of neuroscientists, pharmacologists and clinicians who carried out research with the hope of individuating and proposing an efficacious therapy for this disorder (Sofuoglu, 2010; Kalivas and Volkow, 2011). Unfortunately, although huge efforts, drug dependence is still a relevant health, social and economical problem (Popova et al., 2012; Hiscock et al., 2011; Shorter and Kosten, 2011). Treatments for drug abuse are for the most part ineffective because the molecular and cellular mechanisms through which drugs of abuse alter neuronal circuitry are still unexplained and above all, because drugs of abuse determine a global alteration of cerebral functions that govern behaviour through decision formation, making therefore unfocused the identification of a pharmacological target (Volkow et al., 2011; Schultz 2011). One of the first strategies pursued in drug dependence therapy was directed to removal of pleasure associated with drug taking, but the compliance with the treatment has been always limited, although it could improve when it was supported by psychology based motivational therapy as in alcohol dependence (Krampe and Ehrenreich, 2010; Simkin and Grenoble, 2010). On the other hand it is not infrequent that heavy smokers or heavy drinkers stop suddenly dependence just because their will overcome year-long habits. Decision making is a process based on the interaction between prefrontal cortex (PFC) and subcortical regions involved in reward and motivation, therefore it is likely that failure in self-regulatory behavior, that is common in addicted subjects, could be dependent upon the alteration of interactions between the prefrontal cortex and subcortical regions (Heatherton and Wagner, 2011). In this chapter we will review the role of PFC in addiction with particular attention to dopamine and norepinephrine transmission

Retrospettiva, evoluzioni e applicazioni della sezione aurea

Retrospettiva, evoluzioni e applicazioni della sezione aurea. Analisi delle applicazioni della sezione aurea nell'arte, con particolare riferimento al lavoro di Leonardo Da Vinci

differences in amino acid loss between high efficiency hemodialysis and postdilution and predilution hemodiafiltration using high convection volume exchange a new metabolic scenario a pilot study

Objective The objective of the study was to quantify the loss of total amino acids (TAAs), nonessential amino acids, essential amino acids, and branched chain amino acids (BCAAs) produced by high-efficiency hemodialysis (HEHD), postdilution hemodiafiltration (HDFpost), and predilution hemodiafiltration (HDFpre) using high ultrafiltration volumes; and to define the specific AA losses registered in HEHD, HDFpost, and HDFpre; to identify a potential metabolic and nutritional decline into protein energy wasting; to compare AA analysis of arterial blood samples taken from healthy controls and patients with end-stage renal disease undergoing hemodialysis. Design and Methods Identical dialysis monitors, membranes, and dialysate/infusate were used to homogenize extracorporeal body influence. Ten patients were recruited and randomized to receive treatment with HEHD, HDFpost, and HDFpre it was used on-line dialytic water methodologies (OL); patients' AA arterial concentrations were measured at the start and on completion of dialysis; TAA from the dialyzer filter was calculated, and baseline levels were subsequently compared with findings obtained 1 year later. Finally, the results obtained were compared with the data from a study of 8 healthy volunteers conducted using bioimpedance analysis and laboratory blood tests to assess nutritional status. Results A higher convective dose results in a higher weekly loss of TAA, nonessential AAs, essential AAs, and BCAAs (HEHD: 15.7 g; HDFpost-OL: 16.1 g; HDFpre-OL: 16.3 g, P P Conclusion The study shows that the AA losses in dialytic liquid are greater after high exchange volume HDF techniques, especially HDFpre. The AA losses are not metabolically compensated, so these increase the derangements of predialytic arterial plasma AA levels. Both AA losses and arterial AA perturbations further worsened body composition already after 12 months of additional dialysis

Maternal immune activation disrupts dopamine system in the offspring

Background: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia. Methods: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology. Results: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity. Conclusions: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human patholog

Biodiversity of Sardinian marine caves: sponge fauna = Biodiversità delle grotte marine della Sardegna: la fauna a poriferi

This paper focuses on a faunistic study on sponges from three submerged caves of the Marine Protected Area of Capo Caccia-Isola Piana. Results contribute to the assessment of biodiversity of the scarcely known Sardinian Sea

How to survive and persist in ephemeral water bodies?: the case of sponges (Porifera: Spongillina)

Ephemeral water bodies are subjected to unforeseeable and extreme fluctuations of environmental conditions constraining biodiversity values. Although data are fragmentary and scattered in the literature sponges are known to be able to colonize temporary/intermittent water bodies

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

This work is licensed under a Creative Commons Attribution 4.0 International License.Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus–pituitary–adrenal (HPA) axis

Sintesi ed attività biologica di diossolo[4,5-f]indoli-3-beta-diketoacidi e studi di docking nel sito attivo dell'enzima HIV-1 integrasi

In precedenti comunicazioni stata riportata la sintesi di indoli 2-(3-)-β-diketoacidi 1a-f e 2a,c,e. In questo studio è riportata la sintesi, l'attività  biologica e gli studi di modellistica molecolare condotti sui derivati 2b,d a completamento delle precedenti ricerche