Influence of light at night on allergic diseases: a systematic review and meta-analysis.

BACKGROUND: Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. METHODS: We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. RESULTS: We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. CONCLUSIONS: Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

Circadian rhythmicity in schizophrenia male patients with and without substance use disorder comorbidity.

Circadian rhythmicity is associated to clinical variables that play an important role in both schizophrenia (SZ) and substance use disorders (SUD), although the characteristics of the coexistence of these two diagnoses (SZ +) remain mostly unknown. Hence, we studied a sample of 165 male patients divided in three groups each of 55, according to their diagnoses (SZ + , SZ, and SUD), as well as a healthy control (HC; n = 90) group. Alongside with sociodemographic and clinical variables, circadian rhythms were registered through a sleep-wake data structured interview, a circadian typology questionnaire, and distal skin temperature (DST) using the Thermochron iButton every 2 min during 48 h. Analyses showed that SZ + and SZ patients presented a longer sleep (delay in wake-up time) and mostly an intermediate circadian typology, while SUD patients slept less hours, displaying a morning typology. The DST showed the highest daily activation and stability for the SUD group, even when compared with the HC group. The presence of schizophrenia (SZ + and SZ) was related to a DST pattern with a reduced amplitude determined by a wakefulness impairment, which was more pronounced for SZ patients whose sleep period was adequate. The assessment of circadian rhythms in under treatment male patients with SZ should be focused on the diurnal period as a possible marker of either treatment adherence or patient's recovery, irrespective of the presence of a comorbid SUD. Further research with additional objective measures may provide knowledge transferable to therapeutic strategies and could be useful to establish possible endophenotypes in the future.

Neurocognitive and clinical profile of male patients with substance use disorder in early remission phase with and without comorbid depression.

Substance Use Disorder (SUD) represents one of the most frequent conditions worldwide which commonly coexists with major depressive disorder (MDD). This comorbidity (SUD + MDD) is one of the most prevalent with patients showing certain social and clinical characteristics that could lead to a worsening of their cognitive performance. However, despite these particularities, only a few studies have addressed the possible differences in cognitive performance between patients with SUD + MDD compared with those with SUD-only patients. Therefore, the aim of this study is to examine the clinical and cognitive profile of patients with SUD + MDD vs. SUD-only who are in early remission phase. For this purpose, 271 male patients underwent a clinical and neuropsychological assessment (SUD + MDD group: N = 101; SUD-only group: N = 170). Results indicated that SUD + MDD patients showed worse cognitive performance than SUD in visuospatial reasoning, verbal memory and learning, recognition, and processing speed even after a 3-month period of abstinence. Furthermore, these patients exhibited more self-reported prefrontal symptoms, as well as worse social and clinical conditions. This study indicates that the neurocognitive and clinical profile of patients with SUD + MDD could represent a risk since their characteristics have been associated with poorer recovery and prognosis. Our results could be helpful in clinical practice highlighting the need for cognitive remediation strategies in these populations, providing information that would allow the implementation of more appropriate treatments and preventive strategies.

Circadian functioning and quality of life in substance use disorder patients with and without comorbid schizophrenia.

Sleep disturbances are strongly linked with mental diseases such as substance use disorder (SUD) or schizophrenia (SZ) which can have a detrimental impact on quality of life (QOL), especially when both disorders are comorbid (dual disorder). In absence of studies about both circadian characteristics and QOL in patients with SUD and comorbid SZ (SUD + SZ), we examined a sample of 155 male under treatment, 75 with SUD + SZ and 80 only with SUD. Circadian functioning was evaluated by chronotype, social jet-lag and sleep quality (using the Pittsburgh Sleep Quality Index, PSQI), while the QOL was obtained by the World Health Organization's Quality of Life Questionnaire (WHOQOL)-BREF. SUD + SZ patients were more evening type than SUD, and this chronotype was linked to polydrug use in total sample and SUD + SZ group. We observed that the comorbidity did not lead to worse sleep quality in the SUD and SUD + SZ patients. QOL was poorer in SUD + SZ patients, who showed a negative association of Physical health, Psychological health and Social relationship with suicide attempts and severity of SZ. Lastly, patients with worse QOL also reported poorer sleep quality suggesting that treatment could include circadian adjustments along with a focused approach to lifestyle improvement.

Neuropsychological functioning of patients with major depression or bipolar disorder comorbid to substance use disorders: A systematic review.

Major depression disorder (MDD) and bipolar disorder (BD) are usual comorbidities in patients with substance use disorders (SUD), a condition known as dual disorder (DD). MDD, BD and SUD are associated with cognitive impairment, potentially leading to a greater functional impairment in the context of DD. OBJECTIVES: To review the existing data on the cognitive impairment in DD patients with comorbid MDD or BD, considering the influence of the depressive symptomatology. METHODS: Following the PRISMA protocol 19 studies were selected from the last 17 years, 13 of which focused on BD, five on MDD and one included both diagnoses. RESULTS: Studies based in BD+SUD showed that the most affected cognitive domains were attention and executive functions, but not all of them found a greater impairment due to the comorbidity. While fewer studies were found for depression, MDD+SUD works point to a similar impairment cognitive pattern. Furthermore, depression improvement could be associated to better cognitive performance. LIMITATIONS: More standardized research is needed regarding the influence of depression on cognitive performance of DD patients, especially on those with comorbid MDD. Factors such as main substance, abstinence, or MDD/BD-related variables should be considered. Unstudied factors, like gender or circadian rhythms, are proposed to improve knowledge in this area. CONCLUSIONS: Current studies suggest that DD could potentiate cognitive impairment in BD, MDD and SUD. However, additional research is needed to improve the understanding of comorbidity to apply more individualized therapies in the treatment of these patients, considering the interference of their neurocognitive functioning.

Protocol for Characterization of Addiction and Dual Disorders: Effectiveness of Coadjuvant Chronotherapy in Patients with Partial Response.

This protocol aims to characterize patients with dual disorders (DD; comorbid major depression and schizophrenia) compared with patients with only a diagnosis of substance use disorder (SUD) and those with only a diagnosis of severe mental illness (SMI; major depression and schizophrenia), evaluating clinical and personality characteristics, circadian rhythmic functioning, genetic polymorphism and neuropsychological performance in order to obtain a clinical endophenotype of differential vulnerability for these diagnostic entities. Patients will be divided into three groups: DD (45 men with comorbid schizophrenia, 45 men and 30 women with major depression), SUD (n = 90, with a minimum of 30 women) and SMI males (45 with schizophrenia, 45 with major depression). All patients will be under treatment, with at least three months of SUD abstinence and/or with SMI in remission or with stabilized symptoms. Outpatients of both sexes with insufficient restoration of circadian rhythmicity with SUD (n = 30) and dual depression (n = 30) will be asked to participate in a second two-month study, being alternately assigned to the condition of the chronobiological adjuvant approach to the treatment of regular hour habits and exposure to light or to the usual treatment (control). The effect of the intervention and patient compliance will be monitored with a Kronowise KW6® ambulatory device during the first two weeks of treatment and again at weeks 4 and 8 weeks. After completing the evaluation, follow-up of the clinical evolution will be carried out at 3, 6 and 12 months. This project will allow us to analyze the functional impact of DD comorbidity and to develop the first study of chronobiological therapy in the treatment of SUD and dual depression, with results transferable to the clinical setting with cost-effective recommendations for a personalized approach.

Patients with Schizophrenia Showed Worse Cognitive Performance than Bipolar and Major Depressive Disorder in a Sample with Comorbid Substance Use Disorders.

Comorbidity of substance use disorders (SUD) and severe mental illness (SMI) is highly frequent in patients, the most common diagnoses being schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Since comorbidity has its own clinical features, and neurocognitive functioning is not always similar to psychiatric symptoms the present study explores the cognitive performance of patients with dual disorders. A neuropsychological battery of tests was used to assess 120 under treatment male patients, 40 for each group considered (SZ + SUD, BD + SUD and MDD + SUD) who were mainly polyconsumers. Significant differences (with premorbid IQ as a covariate) were found among the groups, with SZ + SUD having a worse performance in attention, verbal learning, short term memory and recognition. The consideration of a global Z score for performance evidenced an impaired neurocognitive pattern for SZ + SUD compared with BD + SUD and MDD + SUD. According to norms, all patients showed difficulties in verbal learning, short-term memory and recognition. Our research indicated that the neurocognitive functioning of dual disorder patients was influenced by the comorbid SMI, with SZ + SUD presenting major difficulties. Future studies should thoroughly explore the role of such difficulties as indicators or endophenotypes for dual schizophrenia disorders, and their usefulness for prevention and treatment.

The Influence of Artificial Light at Night on Asthma and Allergy, Mental Health, and Cancer Outcomes: A Systematic Scoping Review Protocol.

Artificial light at night (ALAN) exposure is associated with the disruption of human circadian processes. Through numerous pathophysiological mechanisms such as melatonin dysregulation, it is hypothesised that ALAN exposure is involved in asthma and allergy, mental illness, and cancer outcomes. There are numerous existing studies considering these relationships; however, a critical appraisal of available evidence on health outcomes has not been completed. Due to the prevalence of ALAN exposure and these outcomes in society, it is critical that current evidence of their association is understood. Therefore, this systematic scoping review will aim to assess the association between ALAN exposure and asthma and allergy, mental health, and cancer outcomes. This systematic scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We will search bibliographic databases, registries, and references. We will include studies that have described potential sources of ALAN exposure (such as shift work or indoor and outdoor exposure to artificial light); have demonstrated associations with either allergic conditions (including asthma), mental health, or cancer-related outcomes; and are published in English in peer-reviewed journals. We will conduct a comprehensive literature search, title and abstract screening, full-text review, and data collection and analysis for each outcome separately.

Circadian Functioning and Quality of Life in Substance Use Disorder Patients With and Without Comorbid Major Depressive Disorder.

Aim: Although a relationship between circadian disruption and development of several psychiatric disorders, such as major depressive disorder (MDD) and substance use disorder (SUD), has been observed, knowledge on this area is scarce yet. Therefore, this study aims to analyze the circadian functioning and quality of life (QOL) in SUD patients with and without comorbid MDD, two highly prevalent clinical entities with difficult therapeutic management. Methods: One hundred sixty-three male patients under treatment, 81 with SUD and 82 with SUD comorbid major depressive disorder (SUD + MDD), were evaluated. For the circadian functioning assessment, we calculated Social Jet Lag (SJL) and used the reduced Morningness-Eveningness Questionnaire (rMEQ) and the Pittsburgh Sleep Quality Index (PSQI). QOL was measured using the shortened version of the World Health Organization's Quality of Life Questionnaire (WHOQOL-BREF). We collected sociodemographic and clinical variables to evaluate their possible influence on the circadian functioning. Intergroup differences among the variables were examined by different analyses of covariance (ANCOVA and MANCOVA). The possible relationships of quantitative clinical variables with rMEQ, PSQI, and WHOQOL-BREF were explored using bivariate correlation analysis. Results: Lower SJL appears in the SUD + MDD group compared with SUD. The intermediate-type was more prevalent in the SUD group, while a higher percentage of morning-type patients was found in the SUD + MDD. Sleep quality (including latency and daytime dysfunction) was worse for SUD + MDD patients than for SUD even after controlling age and age of SUD onset variables. Last, QOL was poorer in patients with SUD + MDD and, for them, psychological health had a negative relationship with SJL and severity of depression. Conclusions: Our data support and extend previous findings indicating that SUD + MDD is associated with worse clinical characteristics, more sleep problems, and poorer QOL than SUD patients. These results underline the importance of a precise assessment of these measurements in future studies conducted in SUD patients with/without MDD comorbidity that could be considered from a therapeutic point of view.

Premorbid functioning in schizophrenia spectrum disorders with comorbid substance use: A systematic review.

Premorbid functioning has been related with several clinical features and prognosis of schizophrenia spectrum disorders. Comorbidity with substance use is highly prevalent and usually hinders clinical improvement in this kind of psychiatric disorders. This systematic review analyzes the differences in the premorbid functioning of subjects with a schizophrenia spectrum disorder with substance use (SSD+, dual psychosis) or without it (SSD-). A systematic review (PRISMA guidelines), including search in electronic databases (MEDLINE, Web of Science, and Cochrane Library), was performed. 118 published works were considered of which only 20 met our inclusion criteria. Although there is a great variability in methodologies, diagnoses included, and substances used, studies using the Premorbid Functioning Scale to assess the academic and/or social domains found that SSD+ subjects had a poorer academic but better social premorbid functioning than those with SSD-. Current evidence is not conclusive, so additional studies are required to integrate intervening factors in order to clarify the clinical implications of premorbid functioning to improve the course and therapeutic response of patients.

Circadian Characteristics in Patients under Treatment for Substance Use Disorders and Severe Mental Illness (Schizophrenia, Major Depression and Bipolar Disorder).

Dual disorders (substance use and mental illness comorbidity) are a condition that has been strongly associated with severe symptomatology and clinical complications. The study of circadian characteristics in patients with Severe Mental Illness or Substance Use Disorder (SUD) has shown that such variables are related with mood symptoms and worse recovery. In absence of studies about circadian characteristics in patients with dual disorders we examined a sample of 114 male participants with SUD and comorbid Schizophrenia (SZ+; n = 38), Bipolar Disorder (BD+; n = 36) and Major Depressive Disorder (MDD+; n = 40). The possible differences in the sample of patients according to their psychiatric diagnosis, circadian functioning with recordings of distal skin temperature during 48 h (Thermochron iButton®), circadian typology and sleep-wake schedules were explored. MDD+ patients were more morning-type, while SZ+ and BD+ had an intermediate-type; the morning-type was more frequent among participants under inpatient SUD treatment. SZ+ patients had the highest amount of sleeping hours, lowest arousal and highest drowsiness followed by BD+ and MDD+, respectively. These observed differences suggest that treatment for patients with dual disorders could include chronobiological strategies to help them synchronize patterns with the day-light cycle, since morning-type is associated with better outcomes and recovery.

The Influence of Placebo Effect on Craving and Cognitive Performance in Alcohol, Caffeine, or Nicotine Consumers: A Systematic Review.

OBJECTIVE: The present systematic review aims to analyze the evidence about the influence of placebo effect on craving and cognitive performance in alcohol, caffeine, and nicotine consumers. METHODS: Relevant studies were identified via Pubmed, Web of Science, and Scopus databases (up to March 2020). Only those papers published between 2009 and 2019 were searched. RESULTS: Of the 115 preliminary papers, 8 studies of database search and 9 of the manual search were finally included in this review. Findings showed that while alcohol expectancies increased craving, caffeine and nicotine expectancies tend to decrease it. Alcohol expectancies caused similar or slower reaction time when alcohol was not consumed, impairments on inhibitory control (especially after alcohol consumption) and similar post-error slowing. The effect of caffeine and nicotine on reaction time has not been elucidated yet, however, caffeine expectancies have been shown to improve accuracy and the attentional filtering of distracting stimuli. CONCLUSIONS: Alcohol, caffeine, and nicotine expectancies play an important role on craving. Although expectancies produce an effect on cognitive performance, caffeine and nicotine beliefs show an ambiguous impact on reaction time. Only the influence of alcohol expectancies on reaction time has been clarified. Furthermore, caffeine beliefs enhance accuracy.

Health-Related Quality of Life in Male Patients under Treatment for Substance Use Disorders with and without Major Depressive Disorder: Influence in Clinical Course at One-Year Follow-Up.

Health-related quality of life (HRQoL) assessment has interest as an indicator of degree of affectation and prognosis in mental disorders. HRQoL is impaired in both Substance Use Disorder (SUD) and Major Depressive Disorder (MDD), two conditions highly prevalent, although less studied when both are coexisting (SUD + MDD). Hence, we decided to explore HRQoL with the SF-36 survey in a sample of 123 SUD and 114 SUD + MDD patients (51 symptomatic and 63 asymptomatic of depressive symptoms) under treatment. We performed analyses to examine HRQoL among groups, and its predictive value at 3-, 6- and 12-month follow-ups through regression models. Patients with SUD + MDD had worse HRQoL than SUD patients and population norms. For Mental Health, Vitality, and General Health dimensions, lower scores were observed for SUD + MDD regardless the presence/absence of depressive symptoms. For Physical Functioning and Health Change, depressive symptomatology and not the comorbidity of SUD + MDD diagnoses explained HRQoL limitations. At 3-, 6- and 12-month follow-ups we observed two predictors of relapses, General Health for asymptomatic SUD + MDD, and Physical Functioning for SUD. Improving HRQoL in SUD + MDD may be targeted during patient's treatment; future studies should explore the influence of HRQoL on patient's prognosis taking into account the presence/absence of depressive symptomatology.

Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats.

Gammahydroxybutyric acid (GHB) is an endogenous constituent of the central nervous system that has acquired great social relevance for its use as a recreational 'club drug'. GHB, popularly known as 'liquid ecstasy', is addictive when used continuously. Although the symptoms associated with acute intoxication are well known, the effects of prolonged use remain uncertain. We examined in male rats the effect of repeated administration of GHB (10 and 100 mg/kg) on various parameters: neurological damage, working memory and spatial memory, using neurological tests, the Morris water maze and the hole-board test. The results showed that repeated administration of GHB, especially at doses of 10 mg/kg, causes neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories. Stereological quantification showed that this drug produces a drastic neuronal loss in the CA1 hippocampal region and in the prefrontal cortex, two areas clearly involved in cognitive and neurological functions. No effects were noted after quantification in the periaqueductal grey matter (PAG), a region lacking GHB receptors. Moreover, NCS-382, a putative antagonist of GHB receptor, prevented both neurological damage and working- memory impairment induced by GHB. This suggests that the effects of administration of this compound may be mediated, at least partly, by specific receptors in the nervous system. The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects. This is very relevant because its abuse, especially by young persons, could produce considerable neurological alterations after prolonged abuse.

Behavioural profile of selective ligands for mGlu7 and mGlu8 glutamate receptors in agonistic encounters between mice.

Evidence is accumulating for a role of glutamate transmission in aggression modulation. Recent studies indicate that glutamate metabotropic receptors (mGlu1 and mGlu5) are involved in the regulation of aggressive behaviour. However, to date, the possible role of mGlu7 and mGlu8 receptors has not been explored. In this work, we analyze the effect of acute administration of AMN082 (0.5-4 mg/kg, ip) and (S)-3,4-DCPG (2.5-10 mg/kg, ip), selective ligands for the mGlu7 and mGlu8 receptors, respectively, on agonistic encounters between male mice. Individually housed mice were exposed to anosmic opponents 60 or 30 min after drug administration. Ten min of dyadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioural categories was estimated using an ethologically based analysis. The highest dose of AMN082 (4 mg/kg) significantly reduced offensive behaviours (threat and attack), as compared with the control group, without depressing motility, whereas (S)-3,4-DCPG did not produce significant behavioural changes. Overall, these results suggest that mGlu7 receptors (but not mGlu8) may be implicated in the modulation of aggression.

Coping Strategies in Male Patients under Treatment for Substance Use Disorders and/or Severe Mental Illness: Influence in Clinical Course at One-Year Follow-Up.

Coping strategies have an impact on substance use disorders (SUD), relapses, and clinical variables, but knowledge on this area is scarce. We explored the coping strategies used during treatment in patients with dual diagnosis (DD), SUD, and severe mental illness (SMI), and the relation with clinical course and relapses at one-year follow-up. A sample of 223 patients was divided into three groups depending on diagnosis: DD (N = 80; SUD with comorbid schizophrenia or major depressive disorder), SUD only (N = 80), and SMI only (N = 63; schizophrenia or major depressive disorder). MANCOVA analyses reflected differences in self-criticism and problem avoidance, with a higher use of these in the DD and SUD groups. The coping strategies used differed depending on the presence/absence of a SUD, but not depending on psychiatric diagnosis. At one-year follow-up, social support was the only strategy that predicted the presence of relapses in DD patients with schizophrenia (positively), and in SMI patients with major depressive disorder (negatively). Thus, social support was associated with relapses, but the relationship was different depending on psychiatric diagnosis. Further studies should analyze the implications of social support as a coping strategy in different mental disorders, as well as its usefulness in individualized interventions.

JNJ16259685, a selective mGlu1 antagonist, suppresses isolation-induced aggression in male mice.

mGlu1 receptors are present in brain regions involved in aggression modulation. This study examines the effects of 3-4-Dihydro-2H-pyrano[2,3-b]quinolin-7-yl-(cis-4-methoxycyclohexyl)-methanone (JNJ16259685; 0.125, 0.25, 0.5, 1, 2, 4 and 8 mg/kg, i.p), a selective antagonist of the mGlu1 receptors, on agonistic interactions between male mice. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration. Ten minutes of diadic interactions was staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioural categories was estimated using an ethologically based analysis. JNJ16259685 (all doses) produced a significant reduction of offensive behaviours (threat and attack), without affecting immobility. These findings suggest for the first time a role for mGlu1 receptors in aggression regulation.

Effects of SB-205384, a positive modulator of alpha3-subunit-containing GABA-A receptors, on isolation-induced aggression in male mice.

GABA-A receptors are involved in the control of aggressive behaviour. Various studies suggest a role for a1-containing GABA-A receptors in modulating aggression. However, the possible involvement of a3 subunit of GABA-A receptors has not been examined. In this study, we analysed the effect of SB-205384 (0.5-4 mg/kg, i.p), a positive modulator of GABA-A receptors containing a3 subunit, on agonistic behaviour elicited by isolation in male mice. Half of the mice were housed during 30 days and employed as experimental or control animals; the remainder were used as <> and were temporally rendered anosmic by zinc sulphate. Individually housed mice were exposed to anosmic opponents in a neutral area 30 minutes after the drug administration and encounters were videotaped and evaluated using an ethopharmacologically-based analysis. The results indicated that SB-205384 did not produce any significant behavioural changes, suggesting that GABA-A receptors which contain the a3 subunit may not be involved in the modulation of aggression.

Anxiogenic-like effects of gamma-hydroxybutyric acid (GHB) in mice tested in the light-dark box.

Gamma-hydroxybutyric acid (GHB) is a drug with abuse potential, popularly known as "liquid ecstasy". It is an endogenous compound of the mammalian brain which satisfies many of the criteria for consideration as a neurotransmitter or neuromodulator. In this study, the effects of acute administration of GHB (40, 80 and 120 mg/kg, ip) on anxiety, tested in the light/dark box, were examined in male mice of the OF.1 strain. Likewise, we compared the behavioural profile of GHB with that induced by mCPP (1 mg/kg, ip), a compound with known anxiogenic actions. GHB-treated mice spent notably less time in the lit area (40 and 80 mg/kg) and more time in the dark area (all doses), whereas the total number of 'rearings', transitions and latency were significantly reduced. A very similar behavioural profile was observed in mCPP-treated animals. Overall, these findings indicate that GHB exhibits anxiogenic-like properties in male mice. It is suggested that the anxiogenic effects of GHB could be related to its ability to modulate GABA and/or dopaminergic receptors.

Effects of para-methoxyamphetamine (PMA) on agonistic encounters between male mice.

Para-methoxyamphetamine (PMA) is a synthetic drug chemically similar to the recreational drug 3,4-methylenedioxy-methamphetamine (MDMA or "ecstasy") and often replaces MDMA in tablets that show an "ecstasy" logo. PMA displays a higher toxic potential than MDMA, but the behavioral profile of PMA has been scarcely studied in animal models. Here we evaluated the effects of PMA (2, 4, 8, and 12 mg/kg, i.p.) on agonist encounters between male mice using an ethopharmacological approach, the isolation-induced aggression model. Likewise, since PMA and MDMA share common mechanisms of action, we compared the behavioral profile of PMA with that induced by MDMA (8 mg/kg, i.p.) which behavioral effects in this model are well characterized. Individually housed mice were exposed to anosmic standard opponents 30 min after drug administration. The encounters were videotaped and evaluated using an ethologically based analysis. PMA (all doses) significantly reduced offensive behaviors (threat and attack), however, a detailed behavioral analysis suggests that the observed antiaggressive effect seems to be unspecific, showing a complex dose-dependent behavioral profile. Thus, antiaggresive actions observed after the administration of the lowest dose were accompanied by increases in social investigation, avoidance/flee behaviors and non-social explorations, together with a reduction of digging behavior. This pattern reflects both approach-contact behaviors and avoidance-flee behaviors. From 4 mg/kg to 12 mg/kg, the increase in social investigation previously observed disappears, and there is a slight increase in immobility, together with a different behavioral pattern that suggests anxiogenic effects of PMA, similar to those reported after the administration of MDMA. The higher doses of PMA exhibit a behavioral profile very similar to that observed in animals treated with MDMA, with the exception of the immobility produced by PMA. These findings show for the first time the non-specific antiaggressive profile of PMA in the model of aggression induced by isolation in male mice.