Chest Wall Mobility: Identification of Underlying Predictors.

OBJECTIVE: The purpose of this study was to identify factors contributing to normal mobility or hypermobility of the chest wall. METHODS: Seventy-eight young adults were divided into 2 groups: patients with normal mobility (group 1, n = 40) and hypermobility of the chest wall (group 2, n = 38). The mean mobility of the chest wall in groups 1 and 2 was 9.9 and 6.1 cm, respectively. The mean age of groups 1 and 2 was 22.2 and 21.5 years, respectively. The Brief Symptom Inventory, State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale were used to evaluate the psychometric properties. Quality of life was assessed using 12-Item Short Form Health Survey. Smoking status was determined via self-report of current smoking status. Chest wall mobility was measured using thoracic and axillary cirtometry. Pulmonary functions were evaluated using a Spirobank II device. Subsequently, forced vital capacity (FVC), forced expiratory volume in 1 second, peak expiratory flow, and forced expiratory flow 25% to 75% were verified. Carefusion Micro RPM and the 6-minute walk test were used to evaluate maximal respiratory pressures and functional capacity, respectively. RESULTS: With backward linear regression models, FVC and obsessive-compulsive traits were significant predictors of chest wall mobility (R²â€¯= 0.27; P < .001 and P = .01, respectively). In logistic regression models, FVC, maximum inspiratory pressure, and obsessive-compulsive traits were significant predictors of normal mobility/hypermobility of the chest wall (R²â€¯= 0.42; P < .001, P = .01, and P = .03, respectively). CONCLUSION: Forced vital capacity, maximum inspiratory pressure, and obsessive-compulsive traits are significant predictors of chest wall mobility and normal mobility or hypermobility of the chest wall.

Impaired instrumental reversal learning is associated with increased medial prefrontal cortex activity in Sapap3 knockout mouse model of compulsive behavior.

Convergent functional neuroimaging findings implicate hyperactivity across the prefrontal cortex (PFC) and striatum in the neuropathology of obsessive compulsive disorder (OCD). The impact of cortico-striatal circuit hyperactivity on executive functions subserved by these circuits is unclear, because impaired recruitment of PFC has also been observed in OCD patients during paradigms assessing cognitive flexibility. To investigate the relationship between cortico-striatal circuit disturbances and cognitive functioning relevant to OCD, Sapap3 knockout mice (KOs) and littermate controls were tested in an instrumental reversal-learning paradigm to assess cognitive flexibility. Cortical and striatal activation associated with reversal learning was assessed via quantitative analysis of expression of the immediate early gene cFos and generalized linear mixed-effects models. Sapap3-KOs displayed heterogeneous reversal-learning performance, with almost half (n = 13/28) failing to acquire the reversed contingency, while the other 15/28 had similar acquisition as controls. Notably, reversal impairments were not correlated with compulsive grooming severity. cFos analysis revealed that reversal performance declined as medial PFC (mPFC) activity increased in Sapap3-KOs. No such relationship was observed in controls. Our studies are among the first to describe cognitive impairments in a transgenic OCD-relevant model, and demonstrate pronounced heterogeneity among Sapap3-KOs. These findings suggest that increased neural activity in mPFC is associated with impaired reversal learning in Sapap3-KOs, providing a likely neural basis for this observed heterogeneity. The Sapap3-KO model is thus a useful tool for future mechanistic studies to determine how mPFC hyperactivity contributes to OCD-relevant cognitive dysfunction.

Activation of cortical and striatal regions during the expression of a naturalistic compulsive-like behavior in the rabbit.

Nest building behavior in the pregnant rabbit (Oryctolagus cuniculus) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the "straw carrying" phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their "coactivation" during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli.

An extended history of drug self-administration results in multiple sources of control over drug seeking behavior.

It is widely recognized that across the development of drug addiction, cues associated with drug use come to exert increasing control over drug seeking and taking behaviors. However, there remain gaps in our knowledge regarding how the different types of drug related cues affect drug seeking and taking behaviors, and how the emergence of cue control over these behaviors relates to the onset of drug seeking compulsions. This paper reviews the literature on drug self-administration in animals to address these gaps. It first identifies the different types of cues that acquire control over reward seeking behavior generally, and examines whether the same types of cues acquire control over drug seeking behavior specifically. It then examines how the role of drug related cues in motivating and reinforcing drug seeking behavior changes across an extended drug-taking history, with a particular focus on the case of nicotine. The evidence reviewed shows that, after an extended history of drug taking, drug seeking behaviors are controlled by contextual cues associated with the development of drug seeking habits, response contingent cues that accompany delivery of the drug, as well as internal states that correlate with levels of drug intake. These multiple sources of control over drug seeking are discussed in relation to the generation of an addicted phenotype in animal models and the hypothesized progression from internal control over drug use to compulsive drug seeking.

L'hypophyse et ses traitements : comment peuvent-ils influer sur le comportement ?: The pituitary and its treatments: how can they influence behaviour?

Behaviour may be influenced by pituitary hormones or treatments. Dopamine agonist (DA) indicated in prolactinomas treatment can cause side effects, and especially impulse control disorders. In the context of prolactinomas treatment, impulse control disorders (ICD) have been reported like gambling, compulsive shopping, but mostly hypersexuality. These ICD can occur with low AD doses, and seem to be independent of type of molecule and psychiatric medical history. The main pathophysiologic hypothesis is a dysregulation of dopaminergic pathway involved in reward system. Given the possible devastating social impact of these ICD, they have to be screened in patients treated with DA. Our social behaviour can also be impacted by oxytocin. This hormone secreted on physiologic state at posterior pituitary, but also by others areas of brain and brainstem, has an impact on attachment in pair partners and in parent-child relationship, but also in empathy behaviour. Oxytocin affects as well eating behaviour with an anorexigenic impact. Studies on small populations assessed the relevance of an oxytocin treatment in several endocrine and nutritional pathologies like post-surgery craniopharyngioma, panhypopituitarism and obesity. Despite promising results, several pitfalls prevent yet the oxytocin use in clinical practice.

Chronic pramipexole treatment induces compulsive behavior in rats with 6-OHDA lesions of the substantia nigra and ventral tegmental area.

Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions. Accordingly, we aimed to mimic chronic DRT in a PD context, and obtain data on the brain regions that potentially sustain this type of compulsive behavior pattern in rats. We observed that the lesion or treatment alone did not induce compulsive lever pressing in rats. However, rats with lesions of the substantia nigra and ventral tegmental area as well as with chronic PPX treatment developed strong compulsive lever-pressing behavior, as measured via PTSA. Furthermore, when chronic PPX treatment was discontinued before the PTSA test, the lesioned rats showed the same level of compulsive behavior as sham-operated rats. In fact, lesioned, treated, and compulsive-like rats showed significantly higher Fos expression in the orbitofrontal cortex and dorsal striatum. Thus, chronic PPX treatment in PD rats induced a strong compulsive-like behavior. Furthermore, Fos expression mapping suggests that the behavior was sustained via the activation of the orbitofrontal cortex and dorsal striatum.

High-Frequency Stimulation of the Subthalamic Nucleus Blocks Compulsive-Like Re-Escalation of Heroin Taking in Rats.

Opioid addiction, including addiction to heroin, has markedly increased in the past decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction, particularly in individuals who are resistant to traditional therapies. Here we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction. STN HFS prevented the re-escalation of heroin intake after abstinence in rats with extended access to heroin, an animal model of compulsive heroin taking. STN HFS inhibited key brain regions, including the substantia nigra, entopeduncular nucleus, and nucleus accumbens shell measured using brain mapping analyses of immediate-early gene expression and produced a robust silencing of STN neurons as measured using whole-cell recording ex vivo. These results warrant further investigation to examine the therapeutic effects that STN HFS may have on relapse in humans with heroin addiction.

Repetitive transcranial magnetic stimulation to treat substance use disorders and compulsive behavior.

Compulsions, like pathological gambling, binge-eating disorder, alcohol, tobacco or cocaine abuse and compulsive shopping have similar neurophysiological processing. This study aimed to examine the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving patient control over compulsive behavior. The rTMS modulatory role in cortical mesolimbic pathways possibly implies improvement of the inhibitory control system and compulsive consumption drive. Thus, craving reduction would be a component for control achievement. Within this context, 17 studies were found. Most studies applied rTMS over the left dorsolateral prefrontal cortex. Craving reduction was observed in 10 studies and was associated with improved control of compulsion in two of them. In one study reduction in consumption was found without reduction in craving. In addition, improvement in decision making was found in one study.

Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation.

Recent attention has been focused on the long-term impact of cannabis exposure, for which experimental animal studies have validated causal relationships between neurobiological and behavioral alterations during the individual's lifetime. Here, we show that adolescent exposure to Δ(9)-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, results in behavioral and neurobiological abnormalities in the subsequent generation of rats as a consequence of parental germline exposure to the drug. Adult F1 offspring that were themselves unexposed to THC displayed increased work effort to self-administer heroin, with enhanced stereotyped behaviors during the period of acute heroin withdrawal. On the molecular level, parental THC exposure was associated with changes in the mRNA expression of cannabinoid, dopamine, and glutamatergic receptor genes in the striatum, a key component of the neuronal circuitry mediating compulsive behaviors and reward sensitivity. Specifically, decreased mRNA and protein levels, as well as NMDA receptor binding were observed in the dorsal striatum of adult offspring as a consequence of germline THC exposure. Electrophysiologically, plasticity was altered at excitatory synapses of the striatal circuitry that is known to mediate compulsive and goal-directed behaviors. These findings demonstrate that parental history of germline THC exposure affects the molecular characteristics of the striatum, can impact offspring phenotype, and could possibly confer enhanced risk for psychiatric disorders in the subsequent generation.

Acute nicotine administration increases BOLD fMRI signal in brain regions involved in reward signaling and compulsive drug intake in rats.

BACKGROUND: Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine. METHODS: Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03-0.6 mg/kg) on the BOLD signal was investigated for 10 min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated. RESULTS: A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal. CONCLUSIONS: These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.

The role of the cholinergic system in the signal attenuation rat model of obsessive-compulsive disorder.

RATIONALE: In comparison to studies of the involvement of the serotonergic, dopaminergic, and glutamatergic systems in the pathophysiology of obsessive-compulsive disorder (OCD), research on the involvement of the cholinergic system in this disorder has remained sparse. OBJECTIVES: The aim of this study was to test the role of the cholinergic system in compulsive behavior using the signal attenuation rat model of OCD. In this model, "compulsive" behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. METHODS: The acetylcholinesterase inhibitor physostigmine (0.05, 0.10, and 0.15 mg/kg), the nicotinic agonist nicotine (0.03, 0.06, 0.10, 0.30, 0.60, and 1.00 mg/kg), the nicotinic antagonist mecamylamine (1, 3, 5, and 8 mg/kg), the muscarinic agonist oxotremorine (0.0075, 0.0150, and 0.0300 mg/kg), and the muscarinic antagonist scopolamine (0.15, 0.50, 1.00, and 1.50 mg/kg) were acutely administered to rats just before assessing their lever-press responding following signal attenuation (experiments 1, 3, 5, 7, and 9, respectively). Because the effects of signal attenuation are assessed under extinction conditions, drug doses that were effective in the above experiments were also tested in an extinction session of lever-press responding that was not preceded by signal attenuation (experiments 2, 4, 6, 8, and 10). RESULTS: Acute systemic administration of the cholinergic agents did not exert a selective anti- or pro-compulsive effect in the signal attenuation model. CONCLUSIONS: Acetylcholine does not seem to play a role in the signal attenuation rat model of OCD.

Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive-compulsive disorder.

Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.

Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n=10) and the Washers (n=12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals.

Reward circuit function in high BMI individuals with compulsive overeating: similarities with addiction.

CONTEXT: The rising rate of overweight and obese individuals among developing countries despite focused efforts on prevention and treatment underscores not only the need to better define the physiological factors that contribute to weight problems, but also the need to elucidate the neurobiological mechanisms of the self-regulatory failure over eating that leads to weight problems. Emergent findings suggest an overlapping model of addiction and compulsive overeating. OBJECTIVE: Our goal was to examine whether neural hyper-responsivity to reward typically associated with substance abuse could also be seen in individuals exhibiting binge-eating behavior. DESIGN: Participants completed self-assessments of demographic information and eating behavior. Neurofunctional data were collected via functional MRI (fMRI) scans while participants were exposed to personally relevant high-calorie cues. SETTING: The participants were recruited from the general community. PARTICIPANTS: Twenty-six individuals with high body mass index (BMI)>25 and moderate binge-eating behavior as assessed by the Binge Eating Scale (BES) were recruited for this study. MAIN OUTCOME MEASURES: fMRI BOLD response during exposure to high-calorie taste cues. RESULTS: The results showed that exposure to high-calorie taste cues elicited fMRI BOLD response in the reward system of individuals with high BMI, and, more importantly, that this hyper-responsivity increases with greater number of binge-eating symptoms (cluster-corrected p<.05, z=1.9). CONCLUSIONS: These findings support an overlapping neural model of addiction and self-regulatory failure over eating that may lead to problems with weight in humans. These findings offer insight into the prevention and treatment of disordered eating.

Feed-forward mechanisms: addiction-like behavioral and molecular adaptations in overeating.

Food reward, not hunger, is the main driving force behind eating in the modern obesogenic environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences. Important advances have been made to explain mechanisms underlying excessive consumption as an immediate response to presentation of rewarding tastants. However, our understanding of long-term neural adaptations to food reward that oftentimes persist during even a prolonged absence of palatable food and contribute to the reinstatement of compulsive overeating of high-fat high-sugar diets, is much more limited. Here we discuss the evidence from animal and human studies for neural and molecular adaptations in both homeostatic and non-homeostatic appetite regulation that may underlie the formation of a "feed-forward" system, sensitive to palatable food and propelling the individual from a basic preference for palatable diets to food craving and compulsive, addiction-like eating behavior.

Tradução e adaptação para o português do Brasil do Obsessional Beliefs Questionnaire (OBQ-44) / Translation and adaptation into Brazilian Portuguese of the Obsessional Beliefs Questionnaire (OBQ-44)

INTRODUCTION: The Obsessional Beliefs Questionnaire (OBQ-44) is a self-administered instrument comprised of 44 items, designed to assess the beliefs of patients with obsessive compulsive disorder (OCD). The objective of this study was to describe the process of translation and adaption of the questionnaire into Brazilian Portuguese. METHOD: For the translation and adaptation of the OBQ-44, we first obtained authorization from the authors of the original scale to use the instrument. Subsequently, the scale was independently translated from English into Brazilian Portuguese by two health professionals with proficiency in English. Following comparison of the two translations, a preliminary version was obtained and tried out on a sample of 20 patients with a primary diagnosis of OCD. This pretest aimed to assess the patients' understanding of the items and to make any necessary language adaptations. Then, the scale was independently back-translated by two psychiatrists, also with proficiency in English. Following comparison of the two back-translations, a final version in English was developed; this version was evaluated and approved by the authors of the original instrument. RESULTS: The Brazilian Portuguese version of the OBQ-44, after the process of translation and adaptation here described, showed to be of easy interpretation by patients with different educational levels. The instrument can therefore be used to assess patients from different Brazilian socioeconomic contexts. CONCLUSION: OBQ-44 is a self-administered instrument of easy application. Therefore, it can be useful in the identification of dysfunctional beliefs in OCD patients, contributing toward a better understanding of the role played by such beliefs in the onset and maintenance of the disorder.

INTRODUÇÃO: O Obsessional Beliefs Questionnaire (OBQ-44) é um instrumento autorrespondido composto por 44 itens que avaliam as crenças de pacientes com transtorno obsessivo-compulsivo (TOC). O objetivo do presente estudo foi descrever o processo de tradução e adaptação da referida escala para o português do Brasil. MÉTODO: Para o processo de tradução e adaptação do OBQ-44, primeiramente foi obtida licença de uso da escala junto aos autores do instrumento original. Em seguida, a escala foi traduzida de inglês para português brasileiro de forma independente por dois profissionais de saúde com fluência em inglês. Comparando-se as duas escalas traduzidas, obteve-se uma versão preliminar, que foi aplicada a uma amostra de 20 pacientes com diagnóstico principal de TOC, visando observar sua compreensão e realizar adaptações de linguagem. A seguir, a escala foi retrotraduzida de forma independente por dois psiquiatras, também fluentes na língua inglesa. Comparadas as duas retrotraduções, gerou-se uma versão final em língua inglesa; esta versão foi avaliada e aprovada pelos autores do instrumento original. RESULTADOS: A versão em português do Brasil do OBQ-44, após sua tradução e adaptação, demonstrou ser de fácil compreensão por parte de pacientes de diferentes níveis educacionais. Portanto, a escala pode ser utilizada em pacientes das diversas classes econômicas e sociais que caracterizam o Brasil. CONCLUSÃO: O OBQ-44, por ser um instrumento autoaplicável e de fácil compreensão, pode ser útil na identificação de crenças disfuncionais em pacientes com TOC, auxiliando na compreensão do papel dessas crenças na origem e manutenção do transtorno.

Fronto-limbic abnormalities in a patient with compulsive hoarding: a 99mTc-ECD SPECT study.

Little is known about the neuronal mechanism underpinning the pathophysiology of compulsive hoarding. We report the cerebral blood flow changes in an obsessive-convulsive patient with severe hoarding. The patient showed hyperperfusion of the fronto-temporal region and hypoperfusion of the striatal, the middle cingulate and the medial temporal regions during the stage with severe symptoms. Following improvement from the hoarding behaviors, the extent of hypoperfusion was expanded in the bilateral striatum, the anterior and middle cingulate gyrus. The result may substantiate evidence of the fronto-limbic abnormality involved in the pathophysiology of compulsive hoarding.

Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.

Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex.

The quinpirole sensitization model of obsessive-compulsive disorder was used to investigate the functional role that brain regions implicated in a neuroanatomical circuit of obsessive-compulsive disorder may play in compulsive checking behavior. Following repeated injections of saline or quinpirole (0.5mg/kg, twice per week, ×8 injections) to induce compulsive checking, rats received N-methyl-d-aspartate lesions of the nucleus accumbens core (NAc), orbital frontal cortex (OFC) and basolateral amygdala, or sham lesions. When retested at 17days post-surgery, the results showed effects of NAc and OFC but not basolateral amygdala lesion. NAc lesions affected measures indicative of the amount of checking behavior, whereas OFC lesions affected indices of staying away from checking. The pattern of results suggested that the functional roles of the NAc and OFC in checking behavior are to control the vigor of motor performance and focus on goal-directed activity, respectively. Furthermore, similarities in behavior between quinpirole sham rats and saline NAc lesion rats suggested that quinpirole may drive the vigor of checking by inhibition of NAc neurons, and that the NAc may be a site for the negative feedback control of checking.