Enhancement of Behavioral Sensitization, Anxiety-Like Behavior, and Hippocampal and Frontal Cortical CREB Levels Following Cocaine Abstinence in Mice Exposed to Cocaine during Adolescence

Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p.) for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC) and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system. © 2013 Valzachi et al

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproductio

Model Checking of SCADE Designed Systems

International audienceModel checking is a well-known method to verify a formal model in all possible configurations. Nevertheless this technique can hardly scale up to industrial asynchronous systems because of the state-space explosion problem. To address this challenge, a new approach based on context specification (the environment of the system) and an observation engine called OBP (Observer Based Prover) has been developed. The idea is that given a property to be verified, one doesn’t need to explore all possible configurations of the complete system. Among all possible behavior of the system, a tiny part is representative enough for the property to be verified. Thus, specifying a pertinent environment (a context) allows restricting the system behavior on those only parts where the property is worth verifying.The objective of our work is to apply this Context-aware verification method to the verification of SCADE systems designed in LUSTRE language, in order to check behavioral properties related to system safety. Moreover LUSTRE is a synchronous language whereas OBP exploration engine takes as input an asynchronous model designed in FIACRE language. To cope with this problem our approach consists in developing a GALS method combining asynchronous contexts with synchronous models

Partially Bounded Context-Aware Verification

International audienceModel-checking enables the formal verification of software systems. Powerful and automated, this technique suffers, however, from the state-space explosion problem because of the exponential growth in the number of states with respect to the number of interacting components. To address this problem, the Context-aware Verification (CaV) approach decomposes the verification problem using environment-based guides. This approach improves the scalability but it requires an acyclic specification of the verification guides, which are difficult to specify without losing completeness. In this paper, we present a new verification strategy that generalises CaV while ensuring the decomposability of the state-space. The approach relies on a language for the specification of the arbitrary guides, which relaxes the acyclicity requirement, and on a partially-bounded verification procedure. The effectiveness of our approach is showcased through a case-study from the aerospace domain, which shows that the scalability is maintained while easing the conception of the verification guides

Erratum: Lipopolysaccharide-Induced Sickness Behavior in Lactating Rats Decreases Ultrasonic Vocalizations and Exacerbates Immune System Activity in Male Offspring

<b><i>Objective:</i></b> The present study analyzed the effects of lipopolysaccharide (LPS) on maternal behavior during lactation and possible correlations with changes in emotional and immune responses in offspring. <b><i>Methods:</i></b> Lactating rats received 100 μg/kg LPS, and the control group received saline solution on lactation day (LD) 3. Maternal general activity and maternal behavior were observed on LD5 (i.e. the day that the peak of fever occurred). In male pups, hematological parameters and ultrasonic vocalizations (USVs) were assessed on LD5. At weaning, an additional dose of LPS (50 µg/kg, i.p.) was administered in male pups, and open-field behavior, oxidative burst and phagocytosis were evaluated.<b><i> Results: </i></b>A reduction in the time in which dams retrieved the pups was observed, whereas no effects on maternal aggressive behavior were found. On LD5, a reduction of the frequency of USVs was observed in pups, but no signs of inflammation were found. At weaning, an increase in immune system activity was observed, but no differences in open-field behavior were found. <b><i>Conclusion:</i></b> These results indicate that inflammation in lactating mothers disrupted mother/pup interactions and may have produced short- and long-term effects on pup behavior as well as biological pathways that modulate inflammatory responses to bacterial endotoxin challenge in pups