Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice

Organic cation transporters (OCTs) are carrier-type polyspecific permeases known to participate in low-affinity extraneuronal catecholamine uptake in peripheral tissues. OCT3 is the OCT subtype most represented in the brain, yet its implication in central aminergic neurotransmission in vivo had not been directly demonstrated. In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus and cortex. Although OCT3 was found mainly in neurons, it was also occasionally detected in astrocytes in the SNr, hippocampus and several hypothalamic nuclei. In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. The behavioral characterization of these mutants reveal subtle behavioral alterations such as increased sensitivity to psychostimulants and increased levels of anxiety and stress. Altogether our data support a role of OCT3 in the homeostastic regulation of aminergic neurotransmission in the brain.     

Self-reported symptoms of depressed mood, trait anxiety and aggressive behavior in post-pubertal adolescents: Associations with diurnal cortisol profiles

The association between self-reported symptoms and diurnal cortisol profiles was studied in post-puberty adolescents (29 boys and 29 girls, M_age = 15.06 years). The adolescents completed the Children's Depression Inventory, State Trait Anxiety Inventory, and an Aggressive behavior scale. The diurnal cortisol profile was derived from three saliva samples, collected at awakening, noon and evening on a week-end day. Univariate repeated measurement regressions revealed that depressed mood and trait anxiety were strongly and aggressive behavior was weakly related to the diurnal cortisol profile: greater emotional distress was associated with flatter diurnal cortisol profiles. Multivariate analysis, however, revealed that only trait anxiety made an independent contribution. Further analyses suggested that trait anxiety was related to elevated evening cortisol rather than to decreased awakening cortisol and that from a trait anxiety score of 38 onwards, high anxious adolescents show clearly higher evening cortisol than low anxious adolescents. These data suggest that anxiety disorder co-morbidity might explain some of the differences in HPA-axis function among depressed patients.     

Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation

Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).     

SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors

SK3 K(+) channels influence neuronal excitability and are present in 5-hydroxytryptamine (5-HT) and dopamine (DA) nuclei in the brain stem. We therefore hypothesized that SK3 channels affect 5-HT and DA neurotransmission and associated behaviors. To explore this, we used doxycycline-induced conditional SK3-deficient (T/T) mice. In microdialysis, T/T mice had elevated baseline levels of striatal extracellular DA and the metabolites dihydroxyphenylacetic acid and homovanillic acid. While baseline hippocampal extracellular 5-HT was unchanged in T/T mice, the 5-HT response to the 5-HT transporter inhibitor citalopram was enhanced. Furthermore, baseline levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were elevated in T/T mice. T/T mice performed equally to wild type (WT) in most sensory and motor tests, indicating that SK3 deficiency does not lead to gross impairments. In the forced swim and tail suspension tests, the T/T mice displayed reduced immobility compared with WT, indicative of an antidepressant-like phenotype. Female T/T mice were more anxious in the zero maze. In contrast, anxiety-like behaviors in the open-field and four-plate tests were unchanged in T/T mice of both sexes. Home cage diurnal activity was also unchanged in T/T mice. However, SK3 deficiency had a complex effect on activity responses to novelty: T/T mice showed decreased, increased or unchanged activity responses to novelty, depending on sex and context. In summary, we report that SK3 deficiency leads to enhanced DA and 5-HT neurotransmission accompanied by distinct alterations in emotional behaviors.     

Involvement of A2A receptors in anxiolytic,locomotor and motivational properties of ethanol in mice

We have shown previously that mice lacking the adenosine A_2A receptor (A_2AR) generated on a CD1 background self‐administer more ethanol and exhibit hyposensitivity to acute ethanol. We aimed to investigate if the increased propensity of A_2A^?/? mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol. Our results show that A_2A^?/? mice produced on a CD1 background displayed a reduced ethanol‐induced CPP and an increased sensitivity to the anxiolytic and locomotor‐stimulant effects of ethanol, but they did not show alteration in ethanol‐induced CTA and locomotor sensitization. Ethanol‐induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A_2A^?/? mice produced on a C57BL/6J background. Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol‐induced CPP and locomotor‐stimulant effects were not found in knockout mice produced on the alcohol‐preferring C57BL/6J genetic background. Finally, the A_2AR agonist, 2‐p‐(2‐carboxyethyl)‐phenylethylamino‐5′‐N‐ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice. In conclusion, A_2AR deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor‐stimulant/anxiolytic effects of ethanol and a decrease in ethanol‐induced CPP.     

All in for mental health: a pilot study of group therapy for people experiencing anxiety and/or depression and a significant other of their choice

Background A need to provide treatment for people with anxiety and/or depression, and to provide preventive strategies for individuals who love them has been identified. In response, an innovative group therapy programme for people with anxiety and/or depression and a significant other of their choice was developed and implemented.Methods Mixed methods were employed. Five 'significant other' groups were held between May 2005 and June 2006. All group participants were requested to complete the Depression Anxiety Stress Scale (DASS), World Health Organization Quality of Life Assessment (WHOQol) and Connor-Davidson Resilience Scale (CD-RISC), pre- and post-therapy, and three months after their last therapy session. In addition, participants who attended groups between July and September 2005 were invited to provide feedback about the group therapy in an individual semi-structured interview.Results Pilot results indicate positive responses from clients, related to facilitation of knowledge and understanding and skills development. For people referred to the group significant improvements were found in the DASS scores, resilience, psychological health and living environment.Limitations Due to the small sample size, and lack of follow-up data and control group, the findings need to be considered with caution and indicate the necessity to collect further data to provide conclusive findings.Conclusions Overall, the outcome of the 'significant other' pilot programme was useful, in that it facilitated a number of positive outcomes for participants. Areas for further research have been identified including strategies to improve social relationships, the de-identification with the sick/supporter role, and testing this model with diverse populations and clinical groups.     

Caffeine prevents high-intensity exercise-induced increase in enzymatic antioxidant and Na+-K+-ATPase activities and reduction of anxiolytic like-behaviour in rats

Objective: Here we investigated the impact of chronic high-intensity interval training (HIIT) and caffeine consumption on the activities of Na⁺-K⁺-ATPase and enzymes of the antioxidant system, as well as anxiolytic-like behaviour in the rat brain.

Methods: Animals were divided into groups: control, caffeine (4?mg/kg), caffeine (8?mg/kg), HIIT, HIIT plus caffeine (4?mg/kg) and HIIT plus caffeine (8?mg/kg). Rats were trained three times per week for 6 weeks, and caffeine was administered 30 minutes before training. We assessed the anxiolytic-like behaviour, Na⁺-K⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in the brain.

Results and discussion: HIIT-induced anxiolytic-like behaviour increased Na⁺-K⁺-ATPase and GPx activities and TBARS levels, altered the activities of SOD and CAT in different brain regions, and decreased GSH levels. Caffeine, however, elicited anxiogenic-like behaviour and blocked HIIT effects. The combination of caffeine and HIIT prevented the increase in SOD activity in the cerebral cortex and GPx activity in three brain regions. Our results show that caffeine promoted anxiogenic behaviour and prevented HIIT-induced changes in the antioxidant system and Na⁺-K⁺-ATPase activities.     

Ordinary and Recurrent Dream Recall of Active, Past and Non-recurrent Dreamers During and After Academic Stress

The role of stress in the onset and frequency of recurrent dreams was investigated by comparing dream recall of students undergoing naturalistic stress conditions. Thirty nine students in active, past and non-recurrent dream groups (n = 13) recorded frequency of nights per week involving overall and recurrent dream recall in the week prior to mid-term examinations and in a neutral study week in second semester. Self-report measures of everyday hassles and uplifts, anxiety and positive and negative affect experienced during these conditions were also collected. Anxiety and negative affect were reported as significantly higher in the pre-examination week. Overall the groups reported dreams on significantly more nights in the pre-examination week than the post examination week. Recurrent dream nights increased during the stress week for the active recurrent dream group but there was no change in recurrent dream recall for the other groups. These findings are consistent with theories that the experience of emotional stress is a critical factor in the onset and persistence of recurrent dreams.