The relationship between the Met allele of the BDNF Val66Met polymorphism and impairments in decision making under ambiguity in patients with obsessive-compulsive disorder.

Brain-derived neurotrophic factor (BDNF) gene has an important link to neurotransmitter systems, including serotonin, and seems to play a major role in emotional decision making. Impairment of decision making is an important feature of psychiatric disorders such as obsessive-compulsive disorder (OCD). We explore the link between decision making and the BDNF Val66Met polymorphism, which results in a reduction of BDNF activity, in a sample of Caucasian OCD patients. We used the Iowa Gambling Task (IGT) to measure decision making in 122 OCD patients. All patients were assessed using the Yale-Brown Obsessive-Compulsive Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Raven Progressive Matrices. Patients also performed the Continuous Performance Task (CPT-II) and the Trail Making Test (TMT). We grouped Met-allele carriers because these act in a dominant way. Met-allele carries exhibited low performance on both halves of the IGT (first half -F = -2.51, df = 120, P = 0.01; second half -F = -2.32, df = 120, P = 0.02). However, logistic regression analyses showed that the influence of the Met allele seemed to be restricted to the first half of the IGT [first half -ß = 0.55, df = 1, P < 0.01, odds ratio (OR) = 5.62; second half -ß = 0.32, df = 1, P = 0.15, OR = 2.30]. No differences were observed in tests used to evaluate executive functions associated with the dorsolateral prefrontal cortices (TMT and CPT-II, df = 120, P > 0.05 for both). Met-allele impairment may only be related to decisions made under ambiguous conditions. The null results involving TMT and CPT-II are possibly related to the dysfunction of the orbitofrontal cortices that is associated with OCD.

Behavioural changes induced by angiotensin-converting enzyme inhibition during pregnancy and lactation in adult offspring rats.

1. The use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy is contraindicated because of their association with increased risks of fetopathy, including central nervous systems malformations. In addition, some reports have shown that renin-angiotensin system components are expressed differently during embryonic development and adulthood in the rat. 2. Because angiotensin II and its derivative peptides have been implicated in anxiety and modulation of nociception, the aim of the present study was to investigate whether inhibiting ACE during prenatal and neonatal periods would alter behavioural plasticity in adult male offspring rats. 3. Female Wistar rats were treated with captopril (2 mg/mL water; approximately 200 mg/kg per day) during pregnancy and lactation. At adulthood, the offspring were subjected to the open field, elevated plus maze, social interaction, forced swimming and tail flick tests. 4. Perinatal captopril treatment significantly increased ambulation (33%; P < 0.05) and decreased resting time (37.5%; P < 0.05) in the open field test. Perinatal captopril treatment did not alter any of the behavioural parameters of the elevated plus maze; however, captopril treatment did cause a significant increase in social interaction (75.3%; P < 0.05). In the forced swimming test, there was an increased latency period (102.9%; P < 0.001) and a decreased immobility period (38.7, P < 0.05) in rats treated with perinatal captopril. In the tail flick test, perinatal captopril treatment significantly reduced the latency time (26.3%; P < 0.01). 5. The data show that ACE inhibition during prenatal and neonatal periods affects behavioural responses in adult offspring rats, suggesting that ACE is required for the development of neural systems that are associated with adult anxiety and nociceptive behavioural responses.

Noradrenergic stimulation within midbrain raphe increases electrolyte excretion in rats.

The present study was carried out to assess the influence of noradrenergic stimulation of the midbrain dorsal (DRN) and median raphe nuclei (MRN) on urinary volume and electrolyte excretion in hydrated rats. Wistar rats were implanted with a guide cannula into the MRN or DRN and then submitted to two intragastric administrations of water in order to attain an increased diuresis. The following treatments were performed. (1) Intra-DRN microinjections of saline (0.2 microl), alpha(1)-adrenergic agonist phenylephrine (PHE, 0.49 and 4.9 nmol in 0.2 microl), alpha(2)-adrenergic antagonist idazoxan (IDZ, 0.42 and 4.2 nmol in 0.2 microl) or the alpha(1)-adrenergic antagonist prazosin (PRZ, 0.24 and 2.4 nmol in 0.2 microl). (2) Intra-MRN microinjections of saline, IDZ (4.2 nmol in 0.2 microl), PHE (4.9 nmol in 0.2 microl) or PRZ (2.4 nmol in 0.2 microl). Urine samples were subsequently collected over 120 min at 20 min intervals for photometric measurement of sodium and potassium. Intra-DRN administration of PHE and IDZ significantly increased the urinary volume, natriuresis and kaliuresis. Intra-DRN microinjection of a higher dose of PRZ reduced the urinary volume and both sodium and potassium excretion. Intra-MRN microinjections of PHE, IDZ or PRZ did not induce any significant effect on urinary volume or electrolyte excretion. These data suggest that the increase of tonic excitatory noradrenergic input conveyed to DRN influences the hydroelectrolyte homeostasis, possibly through 5-HTergic circuitry.

Antidepressant-like effect of Cecropia glazioui Sneth and its constituents - in vivo and in vitro characterization of the underlying mechanism.

The present study aimed to characterize the antidepressant-like effect of a standardized aqueous extract (AE) of Cecropia glazioui Sneth and its purified fractions on in vivo (forced swimming test), ex vivo (hippocampal monoamines levels) and in vitro (serotonin, noradrenaline and dopamine uptake) tests, searching for the active principles and the underlying mechanisms of action. Treatment with AE, or with its butanolic fraction (BuF), the latter rich in catechins, procyanidins and flavonoids, reduced the immobility of rats in the forced swimming test indicating an antidepressant-like effect. Biochemical analysis of the hippocampal neurotransmitters in BuF-treated rats showed significant increase in monoamines levels. BuF and six of its purified constituents inhibited the uptake of [(3)H]-serotonin, [(3)H]-dopamine and [(3)H]-noradrenaline by synaptosomes of different brain regions. Catechin, catechin (4alpha-->8) ent-catechin (Procyanidin B3 isomer) and epicatechin (4beta-->8) epicatechin (Procyanidin B2) were the most active compounds. Comparatively, the uptake of [(3)H]-noradrenaline was the most affected. These results show that the antidepressant-like effect promoted by C. glazioui extract is most likely due to the blockade of the monoamines uptake in the CNS.

Evaluation of the anxiolytic-like effects of Cecropia glazioui Sneth in mice.

Cecropia glazioui Sneth has been used in most Latin American countries as an antihypertensive, cardiotonic, and antiasthmatic folk medicine. In the cardiovascular studies to define its antihypertensive action it was noteworthy that animals treated with the aqueous extract (AE) of C. glazioui were much calmer than control animals. That observation prompted the present study, aimed at an investigation of the effects of AE and of two semipurified fractions on mouse behavior as evaluated in the elevated plus-maze test (EPM). Male adult Swiss mice were treated with AE (0.25-1 g/kg po) acutely (1 h) or repeatedly (24, 7, and 1.5 h before the test). After repeated administration of AE, the frequency of entries in the open arms of EPM was increased threefold. A similar profile of action was observed after treatment with the butanolic fraction (Fbut) but not with the aqueous fraction (Faq). These findings suggest that the AE of C. glazioui promotes an anxiolytic-like effect in mice. The active principles responsible for this action are present in the less polar fraction of the extract, the main constituents of which are flavonoids and terpenes, among other compounds.