Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats

We investigated the behavioral and molecular interactions between cocaine and nicotine, through evaluating locomotor activity, nicotine intravenous self-administration and gene expression. Locomotor sensitization was induced in male Wistar rats by repeated cocaine (20 mg/kg; i.p.) or saline injections once a day over 7 days. Three days after the last injection, rats were challenged with either saline or cocaine (15 mg/kg; i.p.) and the locomotor activity was measured. The very next day animals received either saline or nicotine (0.4 mg/kg; s.c.) and the locomotor cross-sensitization was tested. Animals were then prepared with intrajugular catheters for nicotine self-administration. Nicotine self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement and a 24-h unlimited access binge. Immediately after the binge sessions animals were decapitated, the brains were removed and the nucleus accumbens was dissected. The dynorphin (DYN), μ-opioid receptor (mu opioid), neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), tropomyosin-related tyrosine kinase B receptor (TrkB) and corticotropin- releasing factor receptor type 1 (CRF-R1) gene expression were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with cocaine caused sensitization of cocaine motor response and locomotor cross-sensitization with nicotine. In the self-administration experiments repeated cocaine administration caused an increase in the nicotine break point and nicotine intake during a 24 h binge session. © 2013 Elsevier Inc.

Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: A role beyond drug seeking in addiction?

Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST. © 2013 IBRO.

Stress-induced reinstatement of amphetamine-conditioned place preference and changes in tyrosine hydroxylase in the nucleus accumbens in adolescent rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Social defeat stress in rats: escalation of cocaine and speedball binge self-administration, but not heroin

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination (speedball).Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.

Multiparticulate systems of pectin-chitosan: Study of swelling and drug release

The aim of this study was to prepare multiparticulate systems of pectin:chitosan (PC:CS) and to evaluate their swelling ratio and the drug release in different environments. PC:CS particles containing triamcinolone were prepared by a complex coacervation/ionotropic gelation method in aqueous environment. The polymer ratio, the calcium concentration and the contact time of the capsules with chitosan dispersion for particles formation and the structures obtained were analyzed. The systems were characterized in relation to morphology, size, swelling, and drug release behavior. The methodology used allowed the production of spherical particles with narrow range of size distribution. The entrapment efficiency for triamcinolone was 84.31 ± 439. It was observed that the particles present a relatively low swelling ratio in acidic medium and a larger swelling ratio in enteric medium. The release profile was dependent on pH and can be related with the swelling ratio.

Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors

An involvement of the transient receptor potential vanilloid (TRPV) 1 channel in the regulation of body temperature (T b) has not been established decisively. To provide decisive evidence for such an involvement and determine its mechanisms were the aims of the present study. We synthesized a new TRPV1 antagonist, AMG0347 [(E)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1- yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide], and characterized it in vitro. We then found that this drug is the most potent TRPV1 antagonist known to increase T b of rats and mice and showed (by using knock-out mice) that the entire hyperthermic effect of AMG0347 is TRPV1 dependent. AMG0347-induced hyperthermia was brought about by one or both of the two major autonomic cold-defense effector mechanisms (tail-skin vasoconstriction and/or thermogenesis), but it did not involve warmth-seeking behavior. The magnitude of the hyperthermic response depended on neither T b nor tail-skin temperature at the time of AMG0347 administration, thus indicating that AMG0347-induced hyperthermia results from blockade of tonic TRPV1 activation by nonthermal factors. AMG0347 was no more effective in causing hyperthermia when administered into the brain (intracerebroventricularly) or spinal cord (intrathecally) than when given systemically (intravenously), which indicates a peripheral site of action. We then established that localized intra-abdominal desensitization of TRPV1 channels with intraperitoneal resiniferatoxin blocks the T b response to systemic AMG0347; the extent of desensitization was determined by using a comprehensive battery of functional tests. We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T b. Copyright © 2007 Society for Neuroscience.

Repeated predictable or unpredictable stress: effects on cocaine-induced locomotion and cyclic AMP-dependent protein kinase activity

Stressful experiences appear to have a strong influence on susceptibility to drug taking behavior. Cross-sensitization between stress and drug-induced locomotor response has been found. Locomotor response to novelty or cocaine (10 mg/kg, i.p.), cyclic AMP-dependent protein kinase (PKA) activity in the nucleus accumbens and basal corticosterone levels were evaluated in male adult rats exposed to acute and chronic predictable or unpredictable stress. Rats exposed to a 14-day predictable stress showed increased locomotor response to novelty and to cocaine, whereas rats exposed to chronic unpredictable stress demonstrated increased cyclic AMP-dependent PKA activity in the nucleus accumbens. Both predictable and unpredictable stress increased basal corticosterone plasma levels. These experiments demonstrated that stress-induced early cocaine sensitization depends on the stress regime and is apparently dissociated from stress-induced changes in cyclic AMP-dependent PKA activity and corticosterone levels. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Effect of cholinergic and adrenergic stimulation of the subfornical organ on water intake

Cholinergic and adrenergic agonists and antagonists were injected directly into the subfornical organ (SFO), via implanted cannulae, and the volume of water ingested was recorded over a period of 1 hour after injection. Application of 2 nmol carbachol caused intense water intake in 100% of the animals (8.78±0.61 ml), with a very short intake latency. When the 2 nmol carbachol dose was preceded by increased doses of atropine, a progressive reduction in water intake was observed, with complete blockage of the thirst-inducing response to carbachol at the 20 nmol dose level with atropine. Followed by several doses of hexamethonium, the water intake caused by application of 2 nmol carbachol was reduced, although the response was not totally blocked. Injection of 80 nmol of nicotine had a significant thirst-inducing inducing effect in 50% of the animals studied (1.06±0.18 ml) and increase in water intake was further reduced by application of increased doses of hexamethonium. Raising the dose levels of noradrenaline into th SFO caused an increase in water intake although to a lesser degree than was observed after carbachol injection. When the 40 nmol dose of noradrenaline was preceded by increased doses of propranolol (5 to 40 nmol), there was a gradual reduction in water intake, with total blockage at the 40 nmol dose. Application of phentolamine in doses of 10 to 80 nmol caused no reduction in water intake after 40 nmol of noradrenaline. Application of isoproterenol at doses from 20 to 160 nmol into the SFO caused a dosedependent increase in water intake which was blocked by previous applications of propranolol. These results support the hypothesis that the water intake caused by chemical stimulation of the SFO is mainly due to muscarinic cholinergic receptors, although the influence of nicotinic receptors or participation of adrenergic mediation should not be ruled out. © 1984.

Vasectomia no sistema público de saúde: Características dos candidatos e variáveis associadas

Objective: This study aimed to characterize candidates undergo vasectomy in the public health system, Araçatuba- SP and to study related variables. Methods: We surveyed 300 medical patients and vasectomized contacted by telephone to assess several characteristics. The variables analyzed for the study were age, marital status, education, religion, monthly family income and per capita, number of living children, reason for seeking treatment method, contraceptive use, marital relationship quality, decision time (date of intent to perform the procedure) and not because of the procedure. Data were pooled for the analysis of results. Results: The age of the candidates ranged from 23 to 65 years (mean 36.86 years) and average 2.56 living sons. The average monthly family income was R$ 1.079,15, with average per capita income of R$ 249,07. The couple's contraception before the procedure was on account of the woman who used oral anti-conception (84%). The complication rate with the method was around 6.04%, the biggest complication was dehiscence (77.7% of cases of complications), these being mainly during the first 100 cases. Conclusion: Vasectomy is a very effective contraceptive method, with low complication rate and low cost, should be encouraged by the public health system as a means of family planning policy.

O comportamento informacional de advogados: um estudo com profissionais que atuam na cidade de Marília e região

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comportamento de busca da informação ambiental por pesquisadores da área de meio ambiente

Pós-graduação em Ciência da Informação - FFC

O uso da informação no âmbito acadêmico: o comportamento informacional de pós-graduandos da área de Educação

This study reports part of a broader research about information behavior of graduate students in Education. The research´s participants were nine masters and doctoral students from a graduate program in Education at a public university. The focus group technique was used to collect the data. The focus group sessions were observed and recorded. The recorded data were transcribed, categorized and then analyzed using the technique of content analysis. The main aspects achieved were: i) Identification’s forms of information resources for research; ii) Internet as source of information; iii) Academic Library’s services and resources use; iv) Training to use of electronic data base; v) Difficulties to perform the search; vi) Advisor’s influence on research development; and vii) Environmental factors that affect information seeking behavior. The main results reveal that the identification of information sources occurs, mainly, through references quoted on studies of the researched area; as well as the advisors’ influence in the information seeking behavior of the participants. The results, also, disclose some environmental aspects, as example, lack of time to search and discomfort caused by the libraries’ environment that influenced negatively the information behavior of the studied group.

Efeitos da pré-exposição ao etanol nos comportamentos relacionados à dependência desta substância e na expressão de CRF1 na amídala em ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)