Pharmacology in vivo of the phenylindan derivative,lu 19-005, a new potent inhibitor of dopamine,noradrenaline and 5-hydroxytryptamine uptake in rat brain

Summary Behavioural effects on dopaminergic transmission of a phenylindane derivative, Lu 19-005 [(±)-trans-3-(3,4-dichlorophenyl)-N-methyl-l-indanamine, HCl], with potent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake in rats and the effect on DA, NA and 5-HT activity in mice have been studied and compared with those of other known DA, NA and 5-HT uptake inhibitors with different selectivity ratios.Lu 19-005 induced stereotyped behaviour after parenteral and oral administration with a duration of action of more than 24 h. The stereotyped licking and biting induced by Lu 19-005 was antagonized by reserpine and cis(Z)-flupentixol, but not affected by prazosin, p-chlorophenylalanine and -methyl-p-tyrosine pretreatments. Metergoline slightly facilitated the onset of stereotypy. Lower doses of Lu 19-005 induced ipsilateral circling in unilaterally 6-hydroxy-DA-lesioned rats. Finally, Lu 19-005 antagonized the catalepsy induced by perphenazine. In mice, Lu 19-005 potentiated the apomorphine-induced gnawing, reversed tetrabenazine-induced ptosis and potentiated the behavioural effects of 5-HTP within a similar dose range.The effects of Lu 19-005 were compared with those of other reference compounds. Nomifensine had qualitatively similar effects in rats although of much shorter duration. In mice, nomifensine selectively reversed tetrabenazine-induced ptosis. Weaker effects in all test models were found with bupropion, LR 5182 and GBR 13.069, compounds with inhibitory effect on DA and NA uptake. The DA-, NA-and 5-HT-uptake inhibitor diclofensine, however, had no effect in rats except in the 6-hydroxy-DA-circling test and had low potency in mice. The specific 5-HT-and NA-uptake inhibitors citalopram and talsupram, respectively, were ineffective in all rat models. They selectively potentiated 5-HTP or reversed tetrabenazine0induced ptosis in mice, respectively, as expected according to their in vitro profile. These results indicate that effect on DA mechanisms are responsible for the behavioural activity of the test compounds in the rat models and that the circling model is the most sensitive. Since DA may be involved in some depressive states Lu 19-005 could be an attaactive new antidepressant as it combines the pharmacological profile of established antidepressants (effect on NA and/or 5-HT uptake) with equipotent activity on DA uptake.     

The effect of the β-carboline FG 7142 on the behaviour of male rats in a living cage: An ethological analysis of social and nonsocial behaviour

The effects of FG 7142, a -carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n=8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self-grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the -carboline inverse agonist.     

The effects of a 5-HT1 receptor ligand isapirone (TVX Q 7821) on 5-HT synthesis and the behavioural effects of 5-HT agonists in mice and rats

The effects of 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-1,2-benzoisothiazol-3(2H)one-1,1-dioxide hydrochloride (isapirone, TVX Q 7821), a putative 5-HT₁ receptor antagonist, has been studied on various models of 5-HT receptor sub-type function. In mice TVX Q 7821 produced a dose-dependent inhibition of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) with an ED₅₀ of 5.3 mg/kg suggesting that TVX Q 7821 was an antagonist of the presynaptic (possibly somato-dendritic) 5-HT_1A receptor. TVX Q 7821 did not alter the locomotor response to the suggested 5-HT_1B agonist RU 24969. The rate of mouse brain 5-HT synthesis was accelerated by TVX Q 7821 (10 mg/kg). 5-HT₂ receptor-mediated head twitch behaviour induced by precursor loading with 5-HTP was unaffected by TVX Q 7821 (10 mg/kg) pretreatment 75 min earlier, but the head-twitch induced by the agonist 5-methoxy-N,N-dimethyltryptamine was enhanced by prior treatment with TVX Q 7821.In rats the hypothermia induced by 8-OH-DPAT was partially antagonised by TVX Q 7821 while the behavioural serotonin syndrome induced by 8-OH-DPAT (a possible post-synaptic 5-HT_1B-mediated effect) was unaffected by TVX Q 7821 as was the locomotion induced by RU 24969.The data suggest that TVX Q 7821 is a good presynaptic 5-HT_1A antagonist in mice, as indicated by the 8-OH-DPAT-induced hypothermia and 5-HT synthesis rate studies. It did not antagonise 5-HT_1B-mediated behaviour in mice or rats and appeared to have an antagonist action at pre- but not post-synaptic 5-HT_1A receptors in rats. Offprint requests to: G.M. Goodwin     

Examining the feasibility,acceptability, validity and reliability of physical activity,sedentary behaviour and sleep measures in people with schizophrenia

BackgroundSchizophrenia is associated with a more than doubled risk of death from cardiovascular disease (CVD). Risk factors for CVD include low levels of physical activity, sedentary behaviour and sleep problems. These risk factors are not systematically assessed by health services.AimsExamine the feasibility, acceptability, validity and reliability of tools measuring physical activity, sedentary behaviour and sleep.MethodsThirty participants with schizophrenia measured their physical activity, sedentary behaviour and sleep by wearing ActiGraph wGT3X-BT accelerometers on their wrist and waist, and recorded their sleep using the SleepBot smartphone app for 7 days. After 7 days they completed the 5-item Simple Physical Activity Questionnaire (SIMPAQ) to retrospectively measure their physical activity and sedentary behaviour over the study period. Concurrent SIMPAQ and SleepBot validity and inter-rater reliability were assessed against accelerometer-derived measures of physical activity, sedentary behaviour and sleep. A qualitative interview was conducted at the end of the study to assess acceptability.ResultsThe tools were feasible: 93% of participants provided valid wear-time accelerometry data and 83% provided SleepBot data. The SIMPAQ showed moderate concurrent validity but poor agreement for moderate-vigorous physical activity (MVPA) and moderate validity and agreement as a measure of sedentary behaviour. The SleepBot app showed poor concurrent validity and agreement for measures of sleep. The qualitative interviews demonstrated the tools were acceptable.ConclusionMonitoring physical activity, sedentary behaviour and sleep by accelerometry, smartphone and questionnaire was feasible and acceptable to people with schizophrenia. The SIMPAQ could be a valid and appropriate tool for routine clinical use.     

Associations between Family-Based Stress and Dietary Inflammatory Potential among Families with Preschool-Aged Children

Chronic stress is known to influence dietary choices, and stressed families often report poorer diet quality; however, little is known about how family-based stress is linked with dietary patterns that promote inflammation. This study investigated associations between family-based stress and the inflammatory potential of the diet among preschool-aged children and their parents. Parents (n = 212 mothers, n = 146 fathers) and children (n = 130 girls, n = 123 boys; aged 18 months to 5 years) from 241 families participating in the Guelph Family Health Study were included in the analyses. Parents reported levels of parenting distress, depressive symptoms, household chaos, and family functioning. The inflammatory potential of parents’ and children’s diets was quantified using the Dietary Inflammatory Index (DII^®), adjusted for total energy intake (i.e., the E-DII^TM). E-DII scores were regressed onto family stress using generalized estimating equations to account for shared variance among family clusters. Compared to those in homes with low chaos, parents in chaotic homes had significantly more proinflammatory dietary profiles (β = 0.973; 95% CI: 0.321, 1.624, p = 0.003). Similarly, compared to those in well-functioning families, parents in dysfunctional families had significantly more proinflammatory dietary profiles (β = 0.967; 95% CI: 0.173, 1.761, p = 0.02). No significant associations were found between parents’ E-DII scores and parenting distress or depressive symptoms, nor were any associations found for children’s E-DII scores. Results were not found to differ between males and females. Parents in chaotic or dysfunctional family environments may be at increased risk of chronic disease due to proinflammatory dietary profiles. Children’s dietary inflammatory profiles were not directly associated with family stress; however, indirect connections through family food-related behaviours may exist. Future research should prioritize elucidating these mechanisms.     

Applying the Stages of Change Model in a Nutrition Education Programme for the Promotion of Fruit and Vegetable Consumption among People with Severe Mental Disorders (DIETMENT)

Despite growing evidence of the benefits of adequate intake of fruit and vegetables (F&V) and the recommendation to consume five servings daily, the adoption of these habits is poor among people with severe mental disorder (SMD). The main aim of the present study is to determine changes in the intake of F&V and motivation to do so among people with SMDs after participating in a food education programme. A community-based randomized controlled trial was conducted in Spain, with the intervention group (IG) participating in a food education programme based on the stages of change model to promote consumption of F&V and the control group (CG) receiving three informative sessions on basic healthy eating. The main outcomes were related to the intake of F&V and stages of change. Data collection was performed at baseline, post intervention, and 12-month follow-up. Seventy-four participants enrolled in the study and sixty completed the 12-month follow-up. An increase in motivation towards the intake of F&V was observed in the IG but not in the CG (McNemar’s test p = 0.016, p = 0.625). No significant difference was observed for the intake of fruit, vegetables, or F&V. Basing food education strategies on the stages of change model shows positive results, increasing the awareness and disposition of people with SMD towards the intake of F&V. More research is needed to identify the most appropriate eating intervention to increase the intake of F&V.     

Enhancing Behavior Change Skills in Health Extension Workers in Ethiopia: Evaluation of an Intervention to Improve Maternal and Infant Nutrition

Maternal and infant nutrition are problematic in areas of Ethiopia. Health extension workers (HEWs) work in Ethiopia’s primary health care system, increasing potential health service coverage, particularly for women and children, providing an opportunity for health improvement. Their roles include improving maternal and infant nutrition, disease prevention, and health education. Supporting HEWs’ practice with ‘non-clinical’ skills in behavior change and health communication can improve effectiveness. This intervention study adapted and delivered a UK-developed training intervention for Health Extension Workers (HEWs) working with the United Nations World Food Programme in Ethiopia. The intervention included communication and behavioral training adapted with local contextual information. Mixed methods evaluation focused on participants’ reaction to training, knowledge, behavior change, and skills use. Overall, 98 HEWs were trained. The intervention was positively received by HEWs. Pre-post evaluations of communication and behavior change skills found a positive impact on HEW skills, knowledge, and motivation to use skills (all p < 0.001) to change women’s nutritional behavior, also demonstrated in role-play scenarios. The study offered substantial learning about intervention delivery. Appropriate cultural adaptation and careful consideration of assessment of psychological constructs are crucial for future delivery.     

Determinants of the Consumption of Regular Soda,Sport, and Energy Beverages in Spanish Adolescents

Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes.     

How different health literacy dimensions influences health and well‐being among men and women: The mediating role of health behaviours

BackgroundHealth literacy, the ability to access, understand, evaluate and apply health information, was found to contribute to positive health outcomes, possibly via promoting healthy behaviours. However, the specific pathways linking different health literacy skills to health and well‐being have remained unclear.MethodsA cross‐sectional survey with structural questionnaires was administered among 2236 adults in Hong Kong (mean age = 46.10 ± 19.05). Health literacy was measured by HLS‐Asian‐47. Participants'' physical conditions and subjective well‐being were predicted by health literacy and health behaviours with structural modelling path analysis.ResultsHealth literacy in finding and understanding information showed a direct effect on enhancing physical health, while applying information capacity had an indirect positive effect via promoting health behaviours, which was moderated by sex. Only among women, this indirect effect predicting fewer physical symptoms and better well‐being was significant.ConclusionsDifferent health literacy dimensions showed distinct direct and indirect pathways in influencing health for men and women. Based on the findings, skill trainings should be developed to enhance both gender''s abilities of finding and understanding health information, while the ability of applying health information should also be improved for modifying lifestyle and promoting health, particularly for women.Patient or Public ContributionTwo thousand and two hundred thirty‐six adults from different districts of Hong Kong participated in the study, and responded to questions on health literacy, behaviours and health status.