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Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions. • Cannabis is the most frequently used illicit drug among pregnant women. • Half of pregnant women who report cannabis use, also report the consumption of alcoholic beverages. • Early alcohol and cannabis exposure is linked to worse developmental outcomes than exposure to either drug alone. • Alcohol and cannabinoids exert a synergistic effect during early development through the endocannabinoid system. [ABSTRACT FROM AUTHOR]

The present study investigated whether neurons in the lateral hypothalamus (LH) play a role in the occurrence of gastric ulcerations induced by cold-water restraint. The first experiment indicated that bilateral N -methyl- d -aspartate (NMDA) lesions of the LH (20 μg/1 μl per side) reduced the amount of gastric ulceration induced by cold-water restraint. In the second experiment, the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV; 2.5 μg/0.5 μl per side) or its vehicle was microinjected bilaterally into the LH prior to the cold-water restraint procedure. APV did not induce gastric ulcerations but reduced the amount of ulceration induced by cold-water restraint. These results indicate that NMDA receptors in the LH play an important role in the occurrence of gastric ulceration induced by cold-water restraint. The participation of the LH and possible neuronal circuitry involved in stress-induced ulceration are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The present study determined whether protein-calorie malnutrition alters anxiety-like behavior in weanling and young adult, male and female malnourished rats. On the day of birth, litters of Wistar rats were divided into Control (C) and Malnutrition (M) groups. In the C group, litters were fed by dams receiving ad libitum lab chow, whereas in the M group, litters were fed by dams receiving 40% of the total amount of the diet offered to dams in the C group. After weaning (PND21) until PND50, animals received the same food as theirs mothers (i.e., ad libitum access in the C group and 40% of the C group food in the M group). On PND21 and PND50, independent C (male [CM] and female [CF]) and M (male [MM] and female [MF]) groups were exposed to the elevated T-maze. The time taken to withdraw four paws from this arm was recorded (baseline latency [BL]). The same measurement was repeated twice at 30s intervals (avoidance trial 1 [AT1] and avoidance 2 [AT2]). The cutoff time in each trial was 300s. ANOVA indicated a four-way age×diet×sex×trials interaction. Post hoc comparisons revealed that PND50 rats had a lower BL and AT1 latency compared with PND21 rats. Training increased both AT1 and AT2 latencies compared with BL in both the CM and CF groups. Weanling malnourished rats exhibited reduced anxiety-like behavior and young adult male rats presented less anxiety-like behavior than young adult female rats in this experimental model. [ABSTRACT FROM AUTHOR]

Abstract: Rats selectively bred for high or low levels of emotionality represent an important and powerful tool to investigate the role of genetic variables in the occurrence of different anxiety disorders. In the present study, albino rats were selectively bred for differences in defensive freezing behavior in response to contextual cues previously associated with footshock, an animal model of general anxiety disorder. The results indicate that these two new lines of rats, which we refer to as Carioca High-Freezing (CHF) and Carioca Low-Freezing (CLF), show a reliable difference in conditioned freezing after three generations of selection. CHF and CLF rats did not present any differences during baseline or post-shock periods. Males from both lines consistently exhibit more conditioned freezing to contextual cues than females. A second experiment used male rats from the fourth generation to investigate the participation of the amygdala during contextual fear conditioning in the CHF and CLF lines. The results indicate that post-training amygdaloid electrolytic lesions lead to similar disruptions in conditioned freezing behavior in both animal lines. [Copyright &y& Elsevier]

Abstract: Background: Since its first definition in the literature, schizoaffective disorder (SAD) has raised a considerable controversy regarding its clinical distinction from schizophrenia (SCH) and mood disorders (MD) as well as its validity as an independent nosological category. Objective: Investigate the validity of SAD as a discrete nosological category and its relationship with SCH and MD. Method: A systematic literature review of clinical trial that compared SAD with SCH and/or MD patients was carried out throughout MEDLINE, psycINFO, Cochrane Library, SCIELO and LILACS databases. Results: Evaluation of demographic characteristics, symptomatology, other clinical data, dexamethasone suppression test, neuroimage exams, response to treatment, evolution and family morbidity indicated that SAD occupies an intermediate position between SCH and MD. Literature review also failed to indicate a clear cut distinction between SAD and SCH or MD. Discussion: Present analysis indicated that SAD cannot be interpreted as atypical forms of SCH or MD. SAD also does not appear to represent a SCH and MD comorbidity or yet an independent mental disorder. It is argued that SAD might constitute a heterogeneous group composed by both SCH and MD patients or a middle point of a continuum between SCH and MD. [Copyright &y& Elsevier]

Abstract: The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms. [Copyright &y& Elsevier]

Gastric mucosal injury induced by body restraint can be enhanced when combined with cold-water immersion. Based on this fact, the present study had two main purposes: (i) to examine the contribution of each of these two forms of stress on the development of gastric ulceration and regulation of body temperature and (ii) to investigate the importance of the animal''s consciousness on gastric ulceration induced by the cold-water restraint. Independent groups of animals were exposed for 3 h to one of the following stressful treatments: body restraint plus cold-water (20+1 °C) immersion, body restraint alone or cold-water immersion alone. Control animals were not exposed to any form of stress. Half of the animals submitted to each of the four treatments were anesthetized with thionembutal (35 mg/kg), whereas the other half was injected with saline. Results indicated that body restraint alone was not sufficient to induce gastric ulceration or changes in body temperature. On the other hand, cold-water exposure, either alone or in conjunction with body restraint, induced the same amount of stomach erosions and hypothermia. Therefore, it appears that body restraint does not play an important role on gastric ulceration induced by the cold-water restraint procedure. Present results also indicated that conscious and anesthetized animals immersed in cold water presented robust gastric ulceration and a marked drop in body temperature. However, conscious animals developed more severe gastric damage in comparison to anesthetized animals although both groups presented the same degree of hypothermia. These findings suggest that hypothermia resulting from cold-water exposure has a deleterious effect on gastric ulceration but the animal''s conscious activity during the cold-water immersion increases the severity of gastric mucosal damage. It is concluded that cold-water restraint is a useful procedure for the study of the underlying mechanisms involved in stress-induced ulceration. [Copyright &y& Elsevier]

• Alzheimer's disease is a neurodegenerative disorder that affects cognitive functions, particularly declarative memory. • Nondeclarative associative learning, such as motor, fear, and emotion-based learning, involve distinct neural structures and are also affected by Alzheimer's disease. • Eyeblink conditioning, fear conditioning, and other emotion-based learning in Alzheimer's disease are investigated in this review. • Evidence suggests that some forms of nondeclarative associative learning such as eyeblink and fear conditioning are impaired in Alzheimer's disease, whereas emotion-based learning may be relatively preserved. • The review highlights the importance of studying nondeclarative associative learning in Alzheimer's disease to better understand the disease progression and develop new intervention strategies. Alzheimer's disease is a neurodegenerative disorder that is characterized by progressive cognitive decline, particularly in declarative memory, and the presence of β-amyloid plaques, neurofibrillary tangles, and cortical atrophy (especially in the temporal lobe). Unlike the relationship between the temporal cortex and declarative memory, nondeclarative memories (e.g., motor, fear, and other emotion-based memories) involve distinct neural structures. The present review investigates nondeclarative associative learning ability in Alzheimer's disease. We discuss eyeblink conditioning, fear conditioning, and other emotion-based learning and present the functions and brain areas that are involved in each type of learning. Evidence suggests that nondeclarative learning is also affected by Alzheimer's disease, although some forms of learning may be relatively preserved. Details about each nondeclarative associative learning process and the implications of these findings are presented. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize Carioca High-conditioned Freezing rats (CHF) regarding their endocrine and metabolic backgrounds. We found an increase in serum corticosterone (CTRL: 96.7 ± 21.65 vs CHF: 292.0 ± 40.71 ng/ml) and leptin (CTRL: 9.5 ± 1.51 vs CHF: 19.2 ± 4.32 ng/ml). Serum testosterone (CTRL: 3.3 ± 0.29 vs CHF: 2.0 ± 0.28 ng/ml) and T3 (CTRL: 52.4 ± 2.74 vs CHF: 42.7 ± 2.94 ng/dl) were decreased in the CHF group, but serum TSH and T4 were unaffected. Body weight and food intake were unchanged, nevertheless retroperitoneal fat (CTRL: 2.2 ± 0.24 vs CHF: 4.8 ± 0.64 g) and epididymal fat (CTRL: 2.6 ± 0.20 vs CHF: 4.8 ± 0.37 g) depot weights were around 2-fold higher in CHF animals. BAT weight was similar in both groups. Serum triglycerides (CTRL: 41.4 ± 6.03 vs CHF: 83.2 ± 17.09 mg/dl) and total cholesterol (CTRL: 181.6 ± 5.61 vs CHF: 226.4 ± 13.04 mg/dl) were higher in the CHF group. Fasting glycemia (CTRL: 68.7 ± 3.04 vs CHF: 82.3 ± 2.99 mg/dl) was also higher in the CHF group, however glucose tolerance test response and serum insulin levels were similar between the groups. Oxygen consumption (CTRL: 10.5 ± 0.40 vs CHF: 7.9 ± 0.58 VO 2 ml/min/kg 0.75 ) and BAT D2 activity (CTRL: 0.7 ± 0.17 vs CHF: 0.3 ± 0.04 fmol T4/min/mg ptn) were lower in the CHF group. Our data show that anxiety could impair endocrine and metabolic functions and may contribute to the development of metabolic diseases. [ABSTRACT FROM AUTHOR]

• Meta-analysis examining CUMS effect on 5-HT receptors expression. • Decreased 5-HT 1A receptor expression is more likely in the frontal cortex. • Cortex and hypothalamus are likely to show altered 5-HT 2A receptors expression. • Evidence of study heterogeneity was found for the 5-HT 2A , but not 5-HT 1A subunit. • We found no clear evidence of between-study publication bias. Chronic-stress-induced depression is recognized as a widespread public health concern. Selective serotonin reuptake inhibitors (SSRIs) have been the most common treatment for this illness. However, the role of 5-hydroxytryptamine (5-HT) receptor subtypes in stress-induced depression remains unclear. Evidence from Animal studies has reported a variety of results regarding the effects of chronic unpredictable mild stress (CUMS) on serotonin signaling pathways and 5-HT receptor subtypes. This divergence may rely on differences in protocols, methods, and studied pathways. Thus, the aim of this systematic review was to weigh the currently available findings regarding serotonin receptor changes in animal models of CUMS. Overall, our meta-analysis results showed the association of altered expression of 5-HT 1A receptors in the frontal cortex and 5-HT 2A receptors both in the whole cortex and the hypothalamus of rats following CUMS. Moreover, by using a qualitative-structured analysis and the application of risk-of-bias tools, we identified possible sources of data variation between the studied literature, which should be taken into account in future animal studies of chronic-stress induced depression. [ABSTRACT FROM AUTHOR]

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg − 1 . INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h after intraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro , anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well. [ABSTRACT FROM AUTHOR]

Diphenyl diselenide ([PhSe] 2 )is an organoselenium compound that has interesting pharmacological properties, including antioxidant, glutathione peroxidase-mimetic, and neuroprotective effects. The objective of the present study was to investigate the possible modulatory effect of (PhSe) 2 in 17th-generation Carioca high-and low-conditioned freezing (CHF and CLF) rats, an animal model of generalized anxiety disorders. (PhSe) 2 was administered at three doses (10, 50, and 100 mg/kg) in CHF and CLF rats, and their anxiety-like profiles (conditioned freezing patterns) were measured before and 30 min after treatment. A significant difference was found in freezing scores between CHF and CLF animals before treatment ( t 70 =12.50, p <0.001). Treatment with (PhSe) 2 at 10 and 50 mg/kg decreased freezing in CHF rats but significantly increased freezing at 100 mg/kg. (PhSe) 2 increased freezing in CLF animals at 50 and 100 mg/kg ( p <0.01). These results indicate that (PhSe) 2 exerts both anxiolytic- and anxiogenic-like effects in bi-directional rat lines. Distinct genetic profiles of the CHF and CLF lines may influence biochemical functions and lead to differential responses to aversive situations and various drugs like (PhSe) 2 . [ABSTRACT FROM AUTHOR]

• CHF and CLF rats are breeding lines based on contextual fear conditioning. • CHF are more strongly affected by chronic stress than CLF animals. • Shifts in defensive coping strategies occur in CHF rats after chronic stress. • Hypercaloric food has a protective effect over the alterations caused by the stress. • These effects are dependent on innate differences in fear response traits. Stress and eating disorders are closely related and are a topic of major concern due to their burden on human health. Engaging in unhealthy eating habits may come as a result of stress, and it often serves to alleviate the symptoms of anxiety or as a distraction from the stressor itself or self-awareness. However, it can also lead to negative feelings of a person's body figure, guilty, or shame. As diverse as these consequences are in humans, so are the effects of the combined administration of stress and hypercaloric food in animals' models. In this study, we assessed the influence of individual innate behavioral predisposition on the effects of chronic unpredictable mild stress and the dietary supplementation with high-sugar/high-fat food. These conditions were applied to male Carioca low- and high-conditioned freezing (CLF and CHF) rats for 21 days. Behavioral results show that the hypercaloric supplement had a protective effect over the alterations caused by the stress. Notably, it was more strongly observed in CHF rather than CLF animals. As the chronic stress led to an impaired behavior in the contextual fear conditioning and the forced swimming tests in the CLF line, animals fed with the HSHF pellet scored responses similar to their untreated control. On CHF rats, these effects also were seen to a broader extent on the open field test, where the locomotor behavior was also increased. No major effects of the diet were seen in the unstressed groups. Overall, our results show that the influences of both chronic stress and hypercaloric feeding depend on innate differences in fear response traits of male Carioca rats. [ABSTRACT FROM AUTHOR]

Background In the last few decades, several tools for studying insight in bipolar disorders have been used. Olaya and colleagues developed the Insight Scale for Affective Disorders (ISAD), which consists of a scale measuring insight through hetero evaluation for patients with mood disorders. The objective of this work is to translate and adapt the original English version of the ISAD to Brazilian Portuguese (ISAD-BR) and to conduct an evaluation of its psychometric properties. Methods Adaptation procedures included translation/back-translation and consultation with a panel of experts. 95 patients with the diagnosis of Type 1 bipolar disorder were evaluated with the final version of the ISAD-BR, which was applied, simultaneously, but independently, by two examiners. Internal consistency and inter-rater reliability were explored and the latent structure of the scale was investigated with principal axis factoring and promax rotation. A second-order factor analysis was conducted to test if the scale had a hierarchical factor structure. Results The ISAD-BR showed good internal consistency and good inter-rater reliability. The analysis pointed to a four-factor solution of the ISAD-BR: awareness of symptoms associated with activity/energy; awareness of having a disorder; awareness of self-esteem and feelings of pleasure; and awareness of social functioning and relationships. The second order factor analysis indicated a hierarchical factor structure for the ISAD-BR, with the four lower-order factors loading on a single higher-order factor. Conclusions Insight into bipolar disorder is a multidimensional construct, covering different aspects of the condition and its symptomatology. Nevertheless, insight about activity/energy changes may be a crucial aspect of insight into bipolar disorder. [ABSTRACT FROM AUTHOR]

Abstract: Background: In the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, the occurrence of increased energy/activity and elation of mood or irritability became necessary symptoms for the diagnosis of an episode of mania or hypomania. Objective: To evaluate whether increases in energy/activity or mood changes represent the core feature of the manic syndrome. Methods: The symptomatology of 117 hospitalized patients with bipolar mania was evaluated using the Schedule for Affective Disorders and Schizophrenia-Changed version (SADS-C). Based on six items of the SADS-S related to mania, a Confirmatory Factor Analysis (CFA) was performed. An Item Response Theory (IRT) analysis was used to identify how much each symptom informs about the different levels of severity of the syndrome. Results: According to the CFA, the item “increased energy” was the symptom with the highest factorial loadings, which was confirmed by the IRT analysis. Thus, increased energy was the alteration most correlated with the total severity of manic symptoms. Additionally, the analysis of the Item Information Function revealed that increased energy was correlated with the larger amplitude of severity levels compared with the other symptoms of mania. Limitations: Only six manic symptoms were considered. The sample might not be representative because the patients were evaluated while presenting peak symptom severity. Conclusions: Increased energy/activity is a more important symptom for a diagnosis of mania than mood changes and represents the core feature of this syndrome. [Copyright &y& Elsevier]

Highlights: [•] Genetic models are powerful tools to help understand anxiety disorders. [•] In order to determine the extent to which multiple anxiety traits generalize we compared eight genetic lines of rats selected for single high or low emotional responses. [•] We find many behavioral traits generalize across different animal lines selected for a single trait. [ABSTRACT FROM AUTHOR]

Abstract: Well-designed screening assessment instruments that can evaluate child development in public daycare centers represent an important resource to help improve the quality of these programs, as an early detection method for early developmental delay. The Ages and Stages Questionnaire, 3rd edition (ASQ-3), comprises a series of 21 questionnaires designed to screen developmental performance in the domains of communication, gross motor skills, fine motor skills, problem solving, and personal–social ability in children aged 2 to 66months. The purpose of the present work was to translate and adapt all of the ASQ-3 questionnaires for use in Brazilian public child daycare centers and to explore their psychometric characteristics with both Classical Test Theory and Rating Scale analyses from the Rasch model family. A total of 18 Ages & Stages Questionnaires — Brazilian translation (ASQ-BR) questionnaires administered at intervals from 6 to 60months of age were analyzed based on primary caregiver evaluations of 45,640 children distributed in 468 public daycare centers in the city of Rio de Janeiro. The results indicated that most of the ASQ-BR questionnaires had adequate internal consistency. Exploratory factor analyses yielded a one-factor solution for each domain of all of the ASQ-BR questionnaires. The only exception was the personal–social domain in some of the questionnaires. Item Response Theory based on Rating Scale analysis (infit and outfit mean squares statistics) indicated that only 44 of 540 items showed misfit problems. In summary, the ASQ-BR questionnaires are psychometrically sound developmental screening instruments that can be easily administered by primary caregivers. [Copyright &y& Elsevier]

Animal models are important tools for studying neuropsychological disorders. Considering their limitations, a more extensive translational research must encompass data that are generated from several models. Therefore, a comprehensive characterization of these models is needed in terms of behavior and neurophysiology. The present study evaluated the behavioral responses of Carioca Low-conditioned Freezing (CLF) rats to haloperidol and methylphenidate. The CLF breeding line is characterized by low freezing defensive responses to contextual cues that are associated with aversive stimuli. CLF rats exhibited a delayed response to haloperidol at lower doses, needing higher doses to reach similar levels of catatonia as control randomly bred animals. Methylphenidate increased freezing responses to conditioned fear and induced motor effects in the open field. Thus, CLF rats differ from controls in their responses to both haloperidol and methylphenidate. Because of the dopamine-related molecular targets of these drugs, we hypothesize that dopaminergic alterations related to those of animal models of hyperactivity and attention disorders might underlie the observed phenotypes of the CLF line of rats. • CLF rats constitute a breeding line based on contextual fear conditioning. • CHF rats have low freezing response in comparison to Control rats. • Methylphenidate increased freezing response and motor activity among CLF rats. • CLF rats exhibited a delayed response to haloperidol at lower doses. • CLF rats might represent an animal model of hyperactivity and attention disorders. [ABSTRACT FROM AUTHOR]

Anxiety is characterized as the emotional response in anticipation of a future threat. This hypervigilant state comprehends a cascade of neuroendocrine and physiological processes, involving the renin-angiotensin system (RAS) and hypothalamic-pituitary-adrenal axis (HPA). Excessive and chronic anxiety may ultimately lead to the development of anxiety disorders. This systematic review aimed to investigate experimental studies using animal models that explored the relationship between RAS and the HPA axis in anxiety disorders. A systematic search was conducted in MEDLINE/PubMed, Embase and Web of Science, and was performed according to PRISMA guidelines. The inclusion criteria was mainly the mention of RAS, HPA axis, and an anxiety disorder in the same study. Quality of studies was evaluated according to the table of risk of bias from SYRCLE. From 12 eligible studies, 7 were included. Research in rats and mice shows that the overactivation of the RAS and HPA axis triggers several neuroendocrine reactions, mainly mediated by AT1 receptors, which promote anxiety-like behaviors and positive feedback for its hyperactivation. On the contrary, the administration of antihypertensive drugs, such as angiotensin AT1 receptor blocker, propitiated the regulation of the RAS and HPA axis, maintaining homeostasis even amid aversive situations. Assessment of risk of bias revealed a pronounced unclear to high risk in several categories, which thus jeopardize the comparability and reproducibility of the results. Nonetheless, the preclinical evidence indicates that the hyperactivation of both RAS and HPA axis during stress exerts deleterious consequences, inducing anxiogenic responses. Moreover, the compiled results show that the modulation of both systems by the administration of AT1 receptor blockers produce anxiolytic effects in animal models and may constitute a new venue for the treatment of anxiety-like disorders. • Systematic review of the interplay between RAS and the HPA axis in anxiety disorders. • Studies showed an unclear risk of bias based on ten categories, varying between 30% and 100%. • Hyperactivation of RAS and the HPA axis triggers anxiety responses in animal models. • AT1 blockers reduce anxiety-like behaviors via modulation of RAS and HPA axis. [ABSTRACT FROM AUTHOR]

It has been suggested that antinociception is part of the animal''s defensive reaction to threatening situations. Chemical or electrical stimulation of the ventrolateral portion of the periaqueductal gray (vlPAG) produces both defensive freezing behavior and antinociception, supporting the view that the vlPAG is a critical structure in the coordination of the defensive reaction. The present study indicated that electrical stimulation of the vlPAG, at a current intensity sufficient to induce defensive freezing, caused a decrease in reactivity to a phasic escapable noxious stimulus (as measured in the tail-flick test) and to a tonic, inescapable noxious stimulus (as measured in the formalin test). These antinociceptive effects were reversed by microinjections of the opioid antagonist naltrexone or the specific 5-HT2A receptor antagonist ketanserin into the stimulation sites. These results suggest that (a) activation of neural circuits of the vlPAG, responsible for the production of freezing behavior, reduces the reactivity to nociceptive stimuli (as evaluated by the tail-flick and formalin tests) and that (b) opioid- and 5-HT2A-mediated mechanisms are called into action for regulating the antinociceptive response that accompanies the freezing behavior induced by vlPAG stimulation. [Copyright &y& Elsevier]

Evidence from clinical and epidemiological studies point towards an association between generalized anxiety disorder (GAD) and alcohol abuse. In the present study we investigated whether a similar relationship could be observed in an animal model of GAD. Specifically, we evaluated the alcohol intake of Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively). Sex differences in alcohol drinking behavior were also studied. Male and female rats from randomized crossbreeding populations served as controls (CTL). Free- and forced-choice protocols were used to measure alcohol consumption, and quinine and saccharin were used as taste control solutions. Our results indicate that CHF rats consumed more alcohol than CLF and CTL ones in both the free-choice (6 and 10% concentrations) and the forced-choice (10% concentration) conditions. CHF female rats exhibited the highest amount of alcohol intake in the forced-choice condition. CHF females also consumed more quinine than CHF male rats. Finally, CHF rats exhibited lower saccharin consumption compared to CLF and CTL animals. Altogether, these results support the hypothesis that there is a positive relationship between anxiety and alcohol intake, and provide further evidence for the use of CHF rats as a model of GAD. • CHF and CLF rat are two bidirectional lines that are based on contextual fear conditioning. • CHF rats have a more anxious phenotype than CLF and control rats. • Anxiety and alcohol use disorders often go together. • CHF rats consumed more alcohol than CLF and control rats. • There was a positive association between anxiety and alcohol intake. • CHF and CLF lines can be a useful genetic model for studying anxiety. [ABSTRACT FROM AUTHOR]

• CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning. • CHF rats have a more "anxious" phenotype than CLF rats in the EPM. • Intraperitoneal injections of midazolam had anxiolytic behavioral effects in CHF and CLF rats. • This pharmacological effect depends on genetic variability associated with basal reactions to threatening situations. • The CHF and CLF breeding lines represent a useful genetic model for studying anxiety. The selective breeding of laboratory rodents with different anxiety-related traits is the subject of growing interest. The present study compared the effects of the benzodiazepine midazolam in the elevated plus maze (EPM) test of anxiety in two lines of Wistar rats that were selectively bred in our laboratory for either high or low anxiety-like traits based on a contextual freezing conditioning paradigm. After phenotyping anxiety-like traits (i.e. , conditioned freezing behavior), Carioca High-Freezing [CHF], Carioca Low-Freezing [CLF]) and control rats were intraperitoneally injected (1.0 ml/kg) with.9 % saline or midazolam (.25,.5,.75, and 1.0 mg/kg) and subjected to the EPM 30 min later. After the saline injection, the CHF and CLF groups exhibited lower and higher open-arm exploration in the EPM, respectively, compared with control rats. These results indicate that anxiety-related traits previously selected from an associative learning paradigm can also be phenotypically expressed in an ethologically based animal model of anxiety. All midazolam doses significantly increased open-arm exploration in both CHF and control animals, but this anxiolytic-like effect in CLF rats was only observed at the lowest dose tested (.25 mg/kg). The present findings indicate that these two breeding lines of rats are a useful model for studying anxiety, and the anxiolytic effect of midazolam depends on genetic variability that is associated with basal reactions to threatening situations. [ABSTRACT FROM AUTHOR]