Compulsive-Like Behaviors of Typical Development: A Question of Their Nature and Continuity with Obsessive-Compulsive Disorder

OBJECTIVE: To investigate compulsive-like behaviors (CLB) of typical development: how they relate to the obsessions and compulsions of obsessive-compulsive disorder (OCD); and the implication of their lingering past 6 years of age (i.e., past their normative, 2-to-5 year, drop). CONCLUSIONS: Findings suggest that normative CLB exist on a continuum (with regard to both symptomatology and functional difficulties) with clinical obsessions and compulsions. With normative repetitive behaviors predicting behavioral perseveration among typically developing individuals aged 6 to 17 years, the present study also suggests that, even in a non-clinical sample, some levels of CLB are maladaptive in middle childhood through adolescence. While studies to date have evaded investigation of high and low CLB in relation to OCD, this latter finding contributes to the growing emphasis upon continuity between typical and atypical development.

Defensive-like behaviors and antinociception induced by NMDA injection into the periaqueductal gray of mice depend on nitric oxide synthesis

Glutamate NMDA receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. Considering that NMDA receptor triggers activation of neuronal nitric oxide synthase (nNOS), enzyme that produces nitric oxide (NO), this study investigated the effects of intra-PAG infusions of NPLA (N omega-propyl-L-arginine), an nNOS inhibitor, on behavioral and antinociceptive responses induced by local injection of NMDA receptor agonist in mice. The behaviors measured were frequency of jumping and rearing as well as duration (in seconds) of running and freezing. Nociception was assessed during the second phase of the formalin test (injection of 50 mu l of formalin 2.5% into the dorsal surface of the right hind paw). Five to seven days after stereotaxic surgery for intracerebral cannula implantation, mice were injected with formalin into the paw, and 10 min later, they received intra-dPAG injection of NPLA (0, 0.2, or 0.4 nmol/0.1 mu l). Ten minutes later, they were injected with NMDA (N-methyl-D-aspartate: 0 or 0.04 nmol/0.1 mu l) into the same midbrain site and were immediately placed in glass holding cage for recording the defensive behavior and the time spent on licking the injected paw with formalin during a period of 10 min. Microinjections of NMDA significantly decreased nociception response and produced jumping, running, and freezing reactions. Intra-dPAG injections of NPLA (0.4 nmol) completely blocked the NMDA effects without affecting either behavioral or nociceptive responses in intra-dPAG saline-injected animals, except for the rearing frequency that was increased by the nNOS inhibitor. These results strongly suggest the involvement of NO within the PAG in the antinociceptive and defensive reactions induced by local glutamate NMDA receptor activation in this midbrain structure. (c) 2006 Elsevier B.V. All rights reserved.

The compulsive-like aspect of the head dipping emission in rats with chronic electrolytic lesion in the area of the median raphe nucleus

Head dipping (HD) is a behavioral pattern considered to have a risk assessment or an exploratory role and is used as a complementary parameter to evaluate anxiety in experimental animals. Since rats with electrolytic lesion in the area of the median raphe nucleus displayed high frequencies of HD in a previous study, the present investigation was undertaken to confirm this observation and to determine its anxiety-related origin. HD episodes were counted in adult male Wistar rats (270-350 g) with electrolytic lesion (N = 11) and sham-lesioned controls (N = 12). When HD was measured for 60 min on an elevated open platform, lesioned rats emitted 13 times more HD than controls (264.7 ± 93.3 vs 20.3 ± 7.6 episodes), with the difference being statistically significant (P < 0.05). HD counts during 10-min sessions held 7, 14, 21, 27, and 63 days after lesion showed significantly higher means (range: 28.14 ± 5.38 to 62.85 ± 9.48) compared to sham-lesioned controls (range: 7.37 ± 1.13 to 8.5 ± 1.45). Normal rats stepped down into their home cages when the vertical distance between them and the cage was short (16 cm), and the step-down latencies increased with increasing depths (36.7 ± 7.92 to 185.87 ± 35.44 s). Lesioned rats showed a similar behavior when facing the shortest depth, but had a significantly increased number (23.28 ± 2.35 episodes) and latency (300 ± 0.00 s) of HD compared to normal rats (9.25 ± 1.37 episodes and 185.87 ± 35.44 s) when facing the greatest depth (30 cm). This suggests that HD may be a depth-measuring behavior related to risk assessment.

Potentiation of panic-like behaviors of the rat by subconvulsive doses of strychnine

The present study was carried out to determine possible panicogenic effects of strychnine administered in subconvulsive doses to rats. Two experiments were conducted to assess two major features of panic in animal models: panic-related flight (through the observation of wild running [WR]) and defensive fights. In the first one, 20 adult male Wistar rats were injected with six different doses of strychnine ranging from 0.5 to 4.0 mg/kg. After 15 min of free observation, the animals were submitted to high-intensity acoustic stimulation and the incidence of WR was recorded. Higher doses of strychnine (above 2.5 mg/kg) easily evoked seizures, but lower doses raised the incidence of WR in a dose-dependent manner. The most effective dose for WR (1.5 mg/kg) was used in the second experiment, in which we investigated the effects of strychnine on sleep-deprivation-induced fights (SDIFs) that have defensive characteristics. For this purpose, 40 subjects were submitted to 5 days of REM-sleep deprivation by the single-platform method and were then assigned into two groups, i.e., strychnine vs. control. After the injections, the animals were observed in social groupings for SDIF recordings over a period of 60 min. The strychnine-treated groups had more SDIF than the control groups (P<.05, Mann-Whitney U test). We conclude that the high level of neural excitability promoted by partial blockade of the glycinergic system can contribute to the manifestation of panic reactions. (C) 2003 Elsevier B.V. All rights reserved.

A Cross-Sectional Survey of Repetitive Behaviors and Restricted Interests in a Typically Developing Turkish Child Population

This study examined compulsive-like behaviors (CLBs) which are higher-order types of Repetitive Behaviors And Restricted Interests (RBRIs) in typically developing children in Turkey. Caregivers of 1,204 children between 8 and 72 months were interviewed with Childhood Routines Inventory (CRI) by trained interviewers in a cross-sectional survey. Factor analysis of the CRI revealed two factor structures comprising "just right behaviors" and "repetitive/sensory sensitivity behaviors". CLB frequency peaked at 2-4 years with declines after age four. In contrast to the previous CRI studies reporting no gender difference, CLBs were more common in males in 12-23 and 48-59 month age groups on both total CLB frequency and repetitive/sensory sensitivity behaviors. Also ages of onsets for CRI items were somewhat later than reported in other samples. Our findings supported the findings of the previous CRI studies while also revealing new perspectives in need of further investigation.

Time spent with children and working parents' willingness to medicate ADHD-like behaviors

ADHD, which refers to one of the most common behavioral problems among children, is subject to controversial arguments surrounding its nature and its primary treatment with psychiatric medications. At the heart of the problem are parents, whose responsibility includes providing pivotal information to clinicians for the diagnosis and deciding whether their children will receive medications. This study investigates the relationship between working parents' willingness to medicate ADHD-like behaviors and the time they are able to spend with their children during a regular workday. The importance of time spent with children derives from the observation that it is likely to influence not only parents' judgments of their children's behaviors but the behaviors themselves. The relationship was investigated using a subsample of 551 working parents (452 parents reporting no child with problems and 99 parents reporting child with problems) drawn from a population-based telephone survey of parents in the Miami-Dade and Broward counties of Florida. A series of path analyses, controlling for selected socio-demographic and family variables, showed that spending more time with their children during a regular workday was significantly related to being less willing to medicate ADHD-like behaviors. The association was stronger for parents reporting having a child with emotional and behavioral problems (β = −.20) and faint for other parents (β = −.06). The interpretation of the study findings emphasizes the vagueness surrounding the nature of ADHD and the events and procedures leading to the diagnosing of a child, as well as the delicate situations in which parents find themselves.

L’accumulation compulsive: Perspectives de l’intervention psychosociale

Cette recherche qualitative a pour objectif de contribuer aux connaissances sur le trouble d’accumulation compulsive (TAC) afin de donner des assises empiriques à la pratique des travailleurs sociaux, techniciens en travail social, éducateurs spécialisés, psychoéducateurs et autres professionnels intervenant au sein des services sociaux. Par extension, elle vise aussi à fournir des pistes pour l’amélioration des services offerts aux personnes aux prises avec ce problème. La question de départ de cette recherche était : Comment les usagers des CSSS ayant eu des services pour un TAC perçoivent et évaluent-ils les interventions effectuées par les intervenants sociaux? Afin d’y répondre, des entrevues individuelles semi-dirigées ont été effectuées auprès d’usagers de Centres de santé et de services sociaux de Québec et ses environs (CSSS Alphonse-Desjardins, Québec-Nord, Portneuf et de la Vieille-Capitale). Ces usagers ont complété le questionnaire Working Alliance Inventory-SR (WAI-SR), version française. Des intervenants sociaux des CSSS ont également participé à des groupes de discussion, afin de compléter et contextualiser les données obtenues. Résultats : Le TAC est une expérience et une situation de vie avant d’être une condition au sens psychiatrique, et les comportements d’accumulation s’inscrivent dans les perceptions que les usagers ont d’eux-mêmes, de leurs priorités et objectifs et des conditions dans lesquelles ils veulent vivre. Les usagers rencontrés ont majoritairement une opinion favorable des services psychosociaux des CSSS, ce qui peut être lié à un bon niveau de reconnaissance de la problématique. La perception favorable des services semble liée à une bonne alliance thérapeutique. Autant les usagers que les intervenants sociaux percevaient qu’il y avait un manque de ressources dans la région de Québec pour répondre aux besoins spécifiques des personnes aux prises avec des problèmes inhérents au TAC. Mots-clés : accumulation compulsive, santé mentale, alliance thérapeutique, intervention psychosociale, perception services, Centre local de services communautaires.

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice

Glutamate-NMDA (N-methyl-D-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g. jumping and running) and antinociception induced by intra-PAG injection of N-methyl-D-aspartate (NMDA) were completely blocked by prior infusion of N(omega)-propyl-L-arginine (NPLA), a specific neuronal nitric oxide synthesis (nNOS) enzyme inhibitor, into the same midbrain structure. It remains unclear however, whether the inhibition of nNOS within the mouse PAG changes the anxiety-like behavior per se or the effects of the inhibition of nNOS depend on the suppression of downstream of glutamate-NMDA receptor activation. This study investigated whether intra-PAG infusion of NPLA (i) attenuates anxiety in the elevated plus-maze (EPM) and (ii) antagonizes the anxiogenic-like effects induced by intra-PAG injection of NMDA. Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that intra-PAG infusions of NPLA (0.2, 0.4 or 0.8 nmol/0.1 mu l) did not alter significantly any behavioral response in the EPM when compared to control group (Experiment 1). Intra-PAG infusion of NMDA (0 and 0.02 nmol/0.1 mu l; a dose that does not provoke vigorous defensive behaviors per se in mice) significantly reduced open arm exploration, confirming an anxiogenic-like effect (Experiment 2). When injected into the PAG 10 min prior local NMDA injection (0.02 nmol/0.1 mu l), NPLA (0.4 nmol/0.1 mu l) was able to revert the anxiogenic-like effect of glutamate-NMDA receptor activation. Neither intra-PAG infusion of NMDA nor NPLA altered closed arm entries, a widely used measure of locomotor activity in the EPM. These results suggest that intra-PAG nitric oxide synthesis does not play a role on anxiety-like behavior elicited during EPM exposure; however its synthesis is important for the proaversive effects produced by activation of glutamate-NMDA receptors located within this limbic midbrain structure. (C) 2008 Elsevier B.V. All rights reserved.

Tonic modulation of anxiety-like behavior by corticotropin-releasing factor (CRF) type 1 receptor (CRF1) within the medial prefrontal cortex (mPFC) in male mice: Role of protein kinase A (PKA)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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)

Central, but not basolateral, amygdala involvement in the anxiolytic-like effects of midazolam in rats in the elevated plus maze

The role of the amygdala in the mediation of fear and anxiety has been extensively investigated. However, how the amygdala functions during the organization of the anxiety-like behaviors generated in the elevated plus maze (EPM) is still under investigation. The basolateral (BLA) and the central (CeA) nuclei are the main input and output stations of the amygdala. In the present study, we ethopharmacologically analyzed the behavior of rats subjected to the EPM and the tissue content of the monoamines dopamine (DA) and serotonin (5-HT) and their metabolites in the nucleus accumbens (NAc), dorsal hippocampus (DH), and dorsal striatum (DS) of animals injected with saline or midazolam (20 and 30 nmol/0.2 mu L) into the BLA or CeA. Injections of midazolam into the CeA, but not BLA, caused clear anxiolytic-like effects in the EPM. These treatments did not cause significant changes in 5-HT or DA contents in the NAc, DH, or DS of animals tested in the EPM. The data suggest that the anxiolytic-like effects of midazolam in the EPM also appear to rely on GABA-benzodiazepine mechanisms in the CeA, but not BLA, and do not appear to depend on 5-HT and DA mechanisms prevalent in limbic structures.

mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats

Background Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague–Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. Results We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. Conclusion This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

Force chains, friction, and flow: Behavior of granular media across length scales

We study the behavior of granular materials at three length scales. At the smallest length scale, the grain-scale, we study inter-particle forces and "force chains". Inter-particle forces are the natural building blocks of constitutive laws for granular materials. Force chains are a key signature of the heterogeneity of granular systems. Despite their fundamental importance for calibrating grain-scale numerical models and elucidating constitutive laws, inter-particle forces have not been fully quantified in natural granular materials. We present a numerical force inference technique for determining inter-particle forces from experimental data and apply the technique to two-dimensional and three-dimensional systems under quasi-static and dynamic load. These experiments validate the technique and provide insight into the quasi-static and dynamic behavior of granular materials.

At a larger length scale, the mesoscale, we study the emergent frictional behavior of a collection of grains. Properties of granular materials at this intermediate scale are crucial inputs for macro-scale continuum models. We derive friction laws for granular materials at the mesoscale by applying averaging techniques to grain-scale quantities. These laws portray the nature of steady-state frictional strength as a competition between steady-state dilation and grain-scale dissipation rates. The laws also directly link the rate of dilation to the non-steady-state frictional strength.

At the macro-scale, we investigate continuum modeling techniques capable of simulating the distinct solid-like, liquid-like, and gas-like behaviors exhibited by granular materials in a single computational domain. We propose a Smoothed Particle Hydrodynamics (SPH) approach for granular materials with a viscoplastic constitutive law. The constitutive law uses a rate-dependent and dilation-dependent friction law. We provide a theoretical basis for a dilation-dependent friction law using similar analysis to that performed at the mesoscale. We provide several qualitative and quantitative validations of the technique and discuss ongoing work aiming to couple the granular flow with gas and fluid flows.