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.

Exposure to chronic stress increases the locomotor response to cocaine and the basal levels of corticosterone in adolescent rats

Repeated exposure to stress results in augmentation in the locomotor response to psychostimulant drugs. We investigated the locomotor response to a novel environment or cocaine [ 10 mg/kg, intraperitoneally (i.p.)] and basal corticosterone levels in male adolescent rats exposed to chronic restraint or variable stress. Animals in the chronic restraint group were restrained for 1 hour daily. The chronic variable stress protocol consisted of exposure to different stressors twice a day in random order. Chronic restraint and variable stress regimens began simultaneously on postnatal day (P) 25 and were applied for 10 days. During this period the control group was left undisturbed except for cleaning the cages. Three days after the last exposure to stress, cocaine- and novelty-induced locomotion were recorded in an activity cage. Plasma corticosterone levels were determined in a subset of stress and control animals. Exposure to both chronic restraint and variable stress increased cocaine- induced locomotion and basal corticosterone plasma levels, while no change was observed in the response to a novel environment. Moreover, rats exposed to variable stress displayed the greatest locomotor response following a challenge dose with cocaine when compared to control and chronic restraint stress groups. This observation indicates that the stress regimen is relevant to the degree of stress-induced sensitization to cocaine.

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.

Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. on day 6 all animals received saline. on day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

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

Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress

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

Context-specific modulation of cocaine-induced locomotor sensitization and ERK and CREB phosphorylation in the rat nucleus accumbens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cocaine-induced behavioral sensitization in adolescent rats endures until adulthood: Lack of association with GluR1 and NR1 glutamate receptor subunits and tyrosine hydroxylase

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

Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

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

A mixture theory based method for three-dimensional modeling of reinforce concrete members with embedded crack finite elements

The paper presents a methodology to model three-dimensional reinforced concrete members by means of embedded discontinuity elements based on the Continuum Strong Discontinuous Approach (CSDA). Mixture theory concepts are used to model reinforced concrete as a 31) composite material constituted of concrete with long fibers (rebars) bundles oriented in different directions embedded in it. The effects of the rebars are modeled by phenomenological constitutive models devised to reproduce the axial non-linear behavior, as well as the bond-slip and dowel action. The paper presents the constitutive models assumed for the components and the compatibility conditions chosen to constitute the composite. Numerical analyses of existing experimental reinforced concrete members are presented, illustrating the applicability of the proposed methodology.

2D evaluation of crack openings using smeared and embedded crack models

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

The surface treatment influence on the fatigue crack propagation of Al 7050-T7451 alloy

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

Describing fatigue crack growth and load ratio effects in Al 2524 T3 alloy with an enhanced exponential model

The fatigue crack behavior in metals and alloys under constant amplitude test conditions is usually described by relationships between the crack growth rate da/dN and the stress intensity factor range Delta K. In the present work, an enhanced two-parameter exponential equation of fatigue crack growth was introduced in order to describe sub-critical crack propagation behavior of Al 2524-T3 alloy, commonly used in aircraft engineering applications. It was demonstrated that besides adequately correlating the load ratio effects, the exponential model also accounts for the slight deviations from linearity shown by the experimental curves. A comparison with Elber, Kujawski and "Unified Approach" models allowed for verifying the better performance, when confronted to the other tested models, presented by the exponential model. (C) 2012 Elsevier Ltd. All rights reserved.

Cocaine mutagenicity and hepatocarcinogenicity evaluations in rodents

The mutagenicity (clastogenicity) and the carcinogenicity (promoting potential) of cocaine were evaluated, respectively, by the mouse bone marrow micronucleus test (study I) and by the initiated rat liver bioassay (study II). In study I, two administration routes (i.p. and i.v.) and two sampling times (24 and 48 hours) after cocaine treatment were studied. Swiss male mice were treated with cocaine at doses of 0, 18, 37, and 75 mg/kg and 0, 2, 4, and 8 mg/kg by i.p. and i.v. routes, respectively. No significant differences were observed between treated and negative control groups regarding the frequencies of micronuclei and the polichromatic/normochromatic erythrocyte (PCE/NCE) ratios. In study II, the development of putative preneoplastic foci of hepatocytes expressing the enzyme glutathione S-transferase placental form (GST-P+) was utilized as the end-point marker in a 8-week rat liver bioassay. The animals were initiated for carcinogenesis by a single i.p. sub-carcinogenic dose of diethylnitrosamine (DEN). After a 6-week exposure to 5 or 10 mg/kg of cocaine i.v. twice a week there was no enhancement of GST-P+ foci development above the values of the control DEN-only treated animals. Also, cocaine did not induce any toxicity as evidenced by the absence of alterations of rat body and liver weights and of liver biochemical function and morphology. The results suggest that cocaine does not have a mutagenic effect on the mouse bone marrow cells or promoting activity on the rat hepatocarcinogenesis process. Teratogenesis Carcinog. Mutagen. 18:199-208, 1998. (C) 1998 Wiley-Liss, Inc.