Effects of the COVID-19 pandemic on mental health, working, and life situation of employees in the Swedish hospitality industry.

Introduction: Previous studies reported that the coronavirus disease (COVID-19) pandemic has negatively affected the mental health of employees in the hospitality industry internationally, however, its effect in Sweden has not been studied. Unlike several other countries, Sweden never enforced a lockdown. Restaurants, bars, and hotels could remain open and host a limited number of guests but had to abide by certain restrictions. Methods: A cross-sectional survey was distributed among hospitality industry employees containing questions regarding the perceived effects of the pandemic on the respondents' working and life situations and their physical and psychological health. The sample consisted of 699 individuals, with a response rate of 47.9%. Results: Although several respondents had been laid off or furloughed, the majority of the sample remained at the same employer. However, more than half of the respondents reported that their economic situation had deteriorated. Compared to before the pandemic, 38.1% experienced elevated levels of stress, 48.3% experienced elevated levels of worry, and 31.4% reported worsened mood. A deteriorating personal economy and difficulty in following COVID-19-related restrictions at work were associated with the worsening of these three mental health aspects. While the fear of becoming infected with COVID-19 was related to higher levels of stress, the fear of infecting others was related to higher levels of worry. Conclusion: Although Sweden imposed less strict measures than most other countries, the personal economy and mental health of hospitality workers were negatively affected by the COVID-19 pandemic.

Feasibility of using breath sampling of non-volatiles to estimate the prevalence of illicit drug use among nightlife attendees.

The prevalence of drug use among nightlife attendees needs to be accurately estimated to, for example, evaluate preventive interventions. This study tested the feasibility of using a breath-sampling device to estimate the prevalence of drug use among nightlife attendees. The study was conducted at five nightclubs and a large music festival in Stockholm, Sweden. Participants were invited to participate and microparticles in exhaled breath were sampled and analyzed for 47 compounds using a state-of-the-art analytic method that follows forensic standards. In addition, participants' breath alcohol concentration was measured and they were interviewed about demographics, drinking habits, and drug use. Of the people invited, 73.7% (n = 1223) agreed to participate, and breath samples were collected from 1204 participants. Breath sampling was fast and well-accepted by participants. 13 percent of participants tested positive for an illicit drug, but only 4.3% self-reported drug use during the last 48 h. The most common substances detected were cocaine, amphetamine, and MDMA. There was no agreement between self-reported and measured use of any drug. Breath sampling is a convenient method to test illicit drug use among a large number of participants at events, and can be used as an estimate of drug use prevalence.

Compliance Checks Decrease Cigarette Sales Rates to Pseudo-Underaged Mystery Shoppers: A Quasi-Experimental Control Group Study.

To control adherence to age limits regarding sales of tobacco products, Swedish authorities can conduct compliance checks. Compliance checks involve prior information to all retailers, mystery shopping, and subsequent feedback to the retailers. This study investigated whether compliance checks can decrease the rates of cigarette sales to underaged adolescents. Test purchases of cigarettes were conducted using pseudo-underaged mystery shoppers, i.e., 18-year-old adolescents with a younger appearance not carrying ID, to measure the refusal rate and rate of ID checks. Test purchases were conducted at 257 retail outlets in 13 municipalities in Stockholm County at baseline 2017 and follow-up 2019, respectively. In between the measurements, six municipalities (intervention area) conducted compliance checks, and seven municipalities were used as a comparison. Comparing baseline and follow-up, rates of refusal (70.4 to 95.8%) and ID checks (80.3 to 95.8%) improved in the intervention area. In the comparison area, refusal rates increased (80.9 to 85.2%), and ID check rates remained stable (at 86.1%). Significant group × time interaction effects reveal that the rates of refusal and ID checks differently changed in the study areas over time. These results indicate that compliance checks are an effective method to decrease cigarette sales to underaged adolescents.

Increasing prevalence of illicit drug use among employees at Swedish workplaces over a 25-year period.

BACKGROUND: Reports indicate that the proportion of adults using drugs of abuse has been increasing in recent years in Europe. Although there are various indicators of increased drug use in Sweden over time, few studies could demonstrate an increase in the proportion of adults using drugs. To investigate changes in drug use prevalence over time, drug testing at the workplace has been used for a 25-year period. METHODS: The urine samples of employees sent by occupational health services from all over Sweden during a 25-year period were analyzed. The analyzing capacity increased over time (from 3411 in 1994 to 60 315 samples analyzed in 2019), and the majority of the samples was analyzed for the following drugs: cannabis (tetrahydrocannabinol), amphetamine, opiates, cocaine, and benzodiazepines. RESULTS: There was an overall increase in the proportion of samples that tested positive for illicit drugs over a 25-year period. This increase seemed to take place step-wise, with phases of linear increases and plateaus that over time became shorter. About 1.3% of samples tested positive for drugs in 1994, whereas 5.6% tested positive in 2019. Since 2007, the rate of positive samples has increased for cannabis and decreased for benzodiazepines. Although the rate of samples tested positive for opiates had remained relatively stable over the last 20 years, this rate had increased for amphetamine and cocaine between 2013 and 2019. CONCLUSION: The results indicate that the use of illicit drugs among employees at Swedish workplaces has increased during a 25-year period.

Illicit Drug Use and Associated Problems in the Nightlife Scene: A Potential Setting for Prevention.

Illicit drug use is prevalent in the nightlife scene, especially at electronic dance music (EDM) events. The aim of the present study was to investigate illicit drug use patterns and consequences of drug use among frequent visitors of EDM events. Young adults (18-34 years old) who had visited at least six EDM events in Sweden during the past year participated in a web-based survey on drug use patterns and its consequences. Fifty-nine percent of participants had used illicit drugs during the past year, most often cannabis followed by ecstasy, cocaine, and amphetamine. Nightlife venues were identified as the main setting for the use of central stimulants, while cannabis was mostly used at home. Frequent alcohol and tobacco use was associated with illicit drug use. The most prevalent negative consequences of drug use were related to mental health, such as impairments in mood, sleep, and memory problems, but physical manifestations were also reported, such as palpitations and collapsing. These findings confirm that drug use is prevalent and associated with negative health effects among EDM nightlife attendees. The nightlife scene is a setting with promising potential to reach a high-risk target group with illicit drug use prevention interventions.

Drug dealing and drug use prevention - a qualitative interview study of authorities' perspectives on two open drug scenes in Stockholm.

BACKGROUND: The use of illicit substances causes various health and social problems globally. Moreover, open drug use and dealing in urban areas, i.e., open drug scenes, can cause public order problems, lead to the recruitment of marginalized and young people for drug use or sale, and induce feelings of insecurity in the general public. Although some international studies have described various ways to manage open drug scenes, such as law enforcement and social interventions, there is limited knowledge about the facilitators and barriers promoting or impeding the implementation of such interventions. The aim of the current study was to explore how different authorities describe the nature of two open drug scenes in Stockholm and to derive authorities' perspective on facilitators and barriers to implementing interventions to reduce open drug dealing, drug use, and related problems at these locations. METHODS: Semi-structured interviews with police officers, security staff, social workers, and municipality officials (n = 21) in the municipality of Stockholm were conducted and analyzed by qualitative content analysis. RESULTS: The analysis of the interviews generated the following categories: Problems, Interventions, Organizational factors, and External factors, revealing information about the strategic and daily counteracting work occurring at the open drug scenes as well as authorities' perceptions of facilitators and barriers to implementing interventions to reduce open drug dealing, drug use, and related problems. Facilitators included motivated and skilled professionals and organized collaboration between key actors. Prominent barriers were a lack of resources to maintain personnel continuity at the scenes, policies that impede information sharing and put security staff in danger, and people who use or sell drugs without having residence permits. CONCLUSIONS: To increase the possibility of successful implementation of interventions to counteract open drug dealing, politicians and authorities should pay attention to collaboration between key actors, sufficient resource allocation, possible modification of policy governing professional duties, and remedies to the vulnerability of individuals without residence permits.

Evaluation of the Implementation of a 25-Year Outdoor School Ground Smoking Ban: A Qualitative Interview Study With Implications for Prevention Practise.

Introduction: Tobacco use, often initiated in younger ages, is a serious health challenge worldwide. In Sweden, smoking has been prohibited on school grounds since 1994. Municipal environmental and health inspectors control the compliance of the ban. Nevertheless, the enforcement and maintenance of the ban are inadequate. The aim of the current study was to identify facilitators, barriers, and the potential for improved implementation of a 25-year outdoor school ground smoking ban in upper secondary schools. Materials and Methods: A process evaluation was conducted using semi-structured interviews with principals in upper secondary schools, local environmental and health inspectors, and local politicians (n = 30) in Stockholm County, with purposive sampling for informant recruitment. A qualitative content analysis of the transcribed interviews was performed. Results: Three main categories and 10 subcategories were generated from the interviews, revealing facilitators, barriers, and the potential for improvement of the implementation of the ban. A prominent facilitator of the ban was informed and engaged principals and inspectors. Prominent barriers were conflicting goals governing the schools, which reduce staffs' motivation to maintain the ban, unclear school ground boundaries, and lack of resources. Potential for improvement was found in a new tobacco act with an extended ban on smoking at school entrances, extended support for schools and staff to strictly enforce the ban, and a continued denormalisation of smoking in society. Conclusion: To achieve effective implementation of outdoor school ground smoking bans in upper secondary schools, authorities need to address conflicts between different goals governing the schools and give necessary support to the staff to strictly enforce the ban. Policies on smoke-free working hours in the municipalities along with tobacco restrictive policies in the surrounding society may increase the possibility to maintain the smoking ban in upper secondary school grounds.

The Importance of Ventral Hippocampal Dopamine and Norepinephrine in Recognition Memory.

Dopaminergic neurons originating from the ventral tegmental area (VTA) and the locus coeruleus are innervating the ventral hippocampus and are thought to play an essential role for efficient cognitive function. Moreover, these VTA projections are hypothesized to be part of a functional loop, in which dopamine regulates memory storage. It is hypothesized that when a novel stimulus is encountered and recognized as novel, increased dopamine activity in the hippocampus induces long-term potentiation and long-term storage of memories. We here demonstrate the importance of increased release of dopamine and norepinephrinein the rat ventral hippocampus on recognition memory, using microdialysis combined to a modified novel object recognition test. We found that presenting rats to a novel object significantly increased dopamine and norepinephrine output in the ventral hippocampus. Two hours after introducing the first object, a second object (either novel or familiar) was placed in the same position as the first object. Presenting the animals to a second novel object significantly increased dopamine and norepinephrine release in the ventral hippocampus, compared to a familiar object. In conclusion, this study suggests that dopamine and norepinephrine output in the ventral hippocampus has a crucial role in recognition memory and signals novelty.

Sales of cigarettes to pseudo-underage mystery shoppers: Experiences from Stockholm County.

Aims: There is an 18 years age limit for cigarette purchase in Sweden and in order to implement this law outlets need to perform ID checks. This study investigates the rate of cigarette sales and ID checks when pseudo-underage mystery shoppers attempted to purchase cigarettes. It explores possible factors associated with sales outcomes. Design: Nine mystery shoppers (6 females and 3 males) attempted to purchase cigarettes without providing ID. The mystery shoppers were 18 years old but had a younger appearance as judged by an expert panel. During each attempt, the adolescents worked in pairs (shopper and observer). A total of 320 outlets in 13 municipalities in Stockholm County were randomly selected based on an outlet type stratum (i.e., gas station, convenience store, kiosk, grocery store). Effects of variables on sales outcomes were analysed using Pearson's chi-square and binominal regression analysis. Results: In 25.4% of the purchase attempts (total n = 287), cigarettes were sold although the pseudo-underage mystery shopper did not provide a valid ID. In 82.6% of the attempts, the shopper was asked to provide ID, and cigarettes were sold in 9.7% of these cases. The rate of sales was significantly higher among female mystery shoppers (29.5%) compared to male (15.0%). Age limit signs were observed in 89.5% of the outlets but they were not significantly associated with the success rate in a regression analysis. Conclusions: The results of the present study indicate that cigarettes could potentially and frequently be sold to underage adolescents by outlets within Stockholm County. Therefore, routines established for checking IDs clearly need to be improved. For example, strategies to improve adherence to the legal age limit on the purchase of cigarettes, such as compliance checks using mystery shopping with feedback to retailers, are needed.

Compliance to the Alcohol Law: Overserving to Obviously Intoxicated Visitors at Music Festivals.

Music festivals are often high-risk settings associated with large numbers of visitors and high alcohol intoxication levels, which contribute to a number of public health-related problems. According to the Swedish Alcohol Act, servers are responsible for not overserving alcohol to obviously intoxicated patrons. The aim of the current study was to examine compliance to the Swedish Alcohol Act at music festivals by assessing the rate of alcohol overserving to festival-goers. We conducted a study at a large music festival in Sweden hosting approximately 50,000 visitors. Professional actors, i.e., pseudo-patrons, enacted a standardized scene in which a highly intoxicated festival-goer attempted to buy beer at licensed premises inside the festival. Observers monitored each attempt. A total of 52 purchase attempts were conducted. The rate of overserving was 26.9% and was not influenced by the server's gender, the number of servers, or the level of crowdedness at the bar area. Overserving differed between server age groups, which was not statistically significant when controlling for other factors. Compliance to the Alcohol Act at the festival can be improved. Intoxication levels and related problems can be reduced by implementing a multicomponent intervention including staff training, policy work, and improved enforcement.

Illicit Drugs in the Nightlife Setting: Changes in Employee Perceptions and Drug Use over a Fifteen-Year Period.

BACKGROUND: Illicit drug use is common in nightlife settings and associated with various public health-related problems, making this an important arena for prevention. Purpose/objectives: To assess perceived prevalence of illicit drug use in the Stockholm nightlife setting, use of and attitudes toward illicit drugs among employees at licensed premises. Also, to make comparisons with two identical measurements from 2001 and 2007/08, and to explore potential differences related to own drug use, type of licensed premise, age or gender. Methods: Cross-sectional surveys were conducted at three time-points: 2001, 2007/08, and 2016/17, comprising employees at licensed premises in Stockholm participating in STAD's Responsible Beverage Service training program. A total of 665 persons (mean age 28 years, 53% women) were included in the 2016/2017 measurement. Results: A majority of the respondents reported having observed patrons intoxicated by illicit drugs in the last six months, and agreed that patrons intoxicated by illicit drugs should be asked to leave licensed premises. The belief that one had observed patrons intoxicated by illicit drugs was more common among respondents who had themselves been using illicit drugs during the last year, and also among employees at nightclubs. Furthermore, comparisons with previous time-points showed a significant increase in the proportion of employees using illicit drugs. Almost half of the respondents in the youngest age group (18-24 years) reported illicit drug use during the last year. Conclusions/importance: Observation and use of illicit drugs are common among employees in the Stockholm nightlife setting and has increased significantly during the past decade.

"How do online and offline sampling compare in a multinational study of drug use and nightlife behaviour?"

BACKGROUND: Online sampling is widely used to recruit hard to reach samples such as drug users at nightlife events. We conducted the first study comparing differences in demographics, drug use and nightlife behaviour between an online sample of young adults engaging with the European nightlife scene, and an offline sample recruited at nightclubs and festivals in Europe. METHODS: Online participants who attended at least six nightlife events in the past 12 months were recruited using social media advertising (May-November 2017). Offline participants were recruited at nightclubs and festivals using a random intercept method (May-November 2017). Samples were compared with respect to age, gender, past year use of alcohol, cannabis, cocaine, ecstasy/MDMA and amphetamines, and past year attendance at nightclubs, licensed festivals, illegal festivals, pubs and house-parties. RESULTS: 6153 online and 3529 offline participants were recruited. When adjusting for differences in age and gender, online participants were less likely to have used each drug and to have attended illegal festivals, pubs and house-parties in the past 12 months. The online sample also used each drug and attended each venue, with the exception of nightclubs, less frequently on average than offline participants. Adjusted odds ratios (range 0.37 to 1.39) and regression coefficients (range -0.84 to 0.07) indicate that the majority of observed differences between the samples were of a small effect size. CONCLUSIONS: Estimates of drug use and nightlife engagement are more conservative when using online sampling compared to venue based sampling. Observed differences were generally small in effect, indicating good overall representativeness when using online sampling in the European nightlife scene.

High levels of alcohol intoxication and strong support for restrictive alcohol policies among music festival visitors.

BACKGROUND: Alcohol intoxication is associated with problems such as violence, injuries, drunk driving and sexual risk-taking, and music festivals are considered a high-risk setting for high levels of alcohol consumption. This study investigates intoxication levels, drinking habits, and opinions on alcohol use and alcohol policies among visitors at one of the largest music festivals in Sweden in 2017. METHODS: A cross-sectional study assessing alcohol intoxication levels was conducted at a music festival (~ 50,000 attendees). Two research teams collected data at the two festival entrances during two nights, from approximately 6:00 pm to 01:30 am. Blood alcohol concentration (BAC) levels were measured using breath analyzers. A face-to-face questionnaire was used to interview attendees about their alcohol use in the past 12 months using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), as well as about their personal opinions on alcohol use and alcohol policies (statement). BAC levels were compared between categories of various factors using Mann-Whitney U test and Kruskal-Wallis test. The distributions of BAC, AUDIT-C and statement category across gender was analyzed using Pearson's Chi-square tests. Associations of BAC levels with different factors were analyzed using Spearman rank correlation and multinomial logistic regression. RESULTS: A total of 1663 attendees were randomly selected and invited to participate, and 1410 consented (63.7% men, 34.9% women, age 16-64 years). The proportion of drinkers was 81%. Among the drinkers, the median BAC level was 0.082%. Thirty-one percent of the participants had a BAC level above 0.10%. Forty-two percent of the participants reported binge drinking monthly, and 20% said that they binge drank weekly. Sixty-three percent of participants reported risky drinking habits. A self-reported risky alcohol habit increased the risk of a high alcohol intoxication level at the festival. Respondents were supportive of restrictive alcohol policies. Men had significantly higher BAC levels, reported more often risky alcohol habits and were less supportive of restrictive alcohol policies than women. CONCLUSIONS: The results indicate that participants at music festivals in Sweden have high levels of alcohol intoxication and largely support restrictive alcohol policies. Thus, there is both a need and support for the implementation of alcohol prevention strategies at festivals.

The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.

Effects of Long-Term Alcohol Drinking on the Dopamine D2 Receptor: Gene Expression and Heteroreceptor Complexes in the Striatum in Rats.

BACKGROUND: Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent. METHODS: A validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naïve control rats. Reverse transcriptase quantitative PCR was used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R, and sigma1 receptor (sigma1R)-D2R. RESULTS: Long-term voluntary alcohol drinking significantly reduced mRNA levels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor complexes in the NAc shell and the dorsal striatum, and decreased the density of sigma1R-D2R heteroreceptor complexes in the dorsal striatum. CONCLUSIONS: The present results on long-term alcohol drinking might reflect reduced D2R levels through reductions in D2R-D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2AR and D2R, an increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2R population within the complex. Hence, both reduced striatal D2R levels and reduced D2R protomer affinity within the striatal A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with AUD. This supports the hypothesis of a hypodopaminergic system in AUD and suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment target.

Alpha7 nicotinic acetylcholine receptor agonists and PAMs as adjunctive treatment in schizophrenia. An experimental study.

Nicotine has been found to improve cognition and reduce negative symptoms in schizophrenia and a genetic and pathophysiological link between the α7 nicotinic acetylcholine receptors (nAChRs) and schizophrenia has been demonstrated. Therefore, there has been a large interest in developing drugs affecting the α7 nAChRs for schizophrenia. In the present study we investigated, in rats, the effects of a selective α7 agonist (PNU282987) and a α7 positive allosteric modulator (PAM; NS1738) alone and in combination with the atypical antipsychotic drug risperidone for their utility as adjunct treatment in schizophrenia. Moreover we also investigated their utility as adjunct treatment in depression in combination with the SSRI citalopram. We found that NS1738 and to some extent also PNU282987, potentiated a subeffective dose of risperidone in the conditioned avoidance response test. Both drugs also potentiated the effect of a sub-effective concentration of risperidone on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. Moreover, NS1738 and PNU282987 enhanced recognition memory in the novel object recognition test, when given separately. Both drugs also potentiated accumbal but not prefrontal risperidone-induced dopamine release. Finally, PNU282987 reduced immobility in the forced swim test, indicating an antidepressant-like effect. Taken together, our data support the utility of drugs targeting the α7 nAChRs, perhaps especially α7 PAMs, to potentiate the effect of atypical antipsychotic drugs. Moreover, our data suggest that α7 agonists and PAMs can be used to ameliorate cognitive symptoms in schizophrenia and depression.

The monoamine stabilizer (-)-OSU6162 counteracts downregulated dopamine output in the nucleus accumbens of long-term drinking Wistar rats.

We recently established that the monoamine stabilizer (-)-OSU6162 (OSU6162) decreased voluntary alcohol-mediated behaviors, including alcohol intake and cue/priming-induced reinstatement, in long-term drinking rats, while blunting alcohol-induced dopamine output in the nucleus accumbens (NAc) of alcohol-naïve rats. Therefore, we hypothesized that OSU6162 attenuates alcohol-mediated behaviors by blunting alcohol's rewarding effects. Here, we evaluated the effects of long-term drinking and OSU6162 treatment (30 mg/kg, sc) on basal and alcohol-induced (2.5 g/kg, ip) NAc dopamine outputs in Wistar rats after 10 months of intermittent access to 20% alcohol. The results showed that basal and alcohol-induced NAc dopamine outputs were significantly lower in long-term drinking rats, compared with alcohol-naïve rats. In the long-term drinking rats, OSU6162 slowly increased and maintained the dopamine output significantly elevated compared with baseline for at least 4 hours. Furthermore, OSU6162 pre-treatment did not blunt the alcohol-induced output in the long-term drinking rats, a finding that contrasted with our previous results in alcohol-naïve rats. Finally, OSU6162 did not induce conditioned place preference (CPP) in either long-term drinking or alcohol-naïve rats, indicating that OSU6162 has no reinforcing properties. To verify that the CPP results were not due to memory acquisition impairment, we demonstrated that OSU6162 did not affect novel object recognition. In conclusion, these results indicate that OSU6162 attenuates alcohol-mediated behaviors by counteracting NAc dopamine deficits in long-term drinking rats and that OSU6162 is not rewarding on its own. Together with OSU6162's beneficial side-effect profile, the present study merits evaluation of OSU6162's clinical efficacy to attenuate alcohol use in alcohol-dependent patients.

Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats.

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression.

Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson's disease: comparison with the effects produced by L-DOPA and an MAO-B inhibitor.

The most effective treatment of Parkinson's disease (PD) L-DOPA is associated with major side effects, in particular L-DOPA-induced dyskinesia, which motivates development of new treatment strategies. We have previously shown that chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA, produced equal anti-parkinsonian effect and reduced dyskinesia in 6-OHDA-lesioned rats. The advantageous effects of D3-L-DOPA are in all probability related to a reduced metabolism of deuterium dopamine by the enzyme monoamine oxidase (MAO). Therefore, a comparative neurochemical analysis was here performed studying the effects of D3-L-DOPA and L-DOPA on dopamine output and metabolism in 6-OHDA-lesioned animals using in vivo microdialysis. The effects produced by D3-L-DOPA and L-DOPA alone were additionally compared with those elicited when the drugs were combined with the MAO-B inhibitor selegiline, used in PD treatment. The different treatment combinations were first evaluated for motor activation; here the increased potency of D3-L-DOPA, as compared to that of L-DOPA, was confirmed and shown to be of equal magnitude as the effect produced by the combination of selegiline/L-DOPA. The extracellular levels of dopamine were also increased following both D3-L-DOPA and selegiline/L-DOPA administration compared with L-DOPA administration. The enhanced behavioral and neurochemical effects produced by D3-L-DOPA and the combination of selegiline/L-DOPA are attributed to decreased metabolism of released dopamine by MAO-B. The similar effect produced by D3-L-DOPA and selegiline/L-DOPA, respectively, is of considerable clinical interest since D3-L-DOPA, previously shown to exhibit a wider therapeutic window, in addition may reduce the need for adjuvant MAO-B inhibitor treatment.

The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents.

Development of alcohol use disorders largely depends on the effects of alcohol on the brain reward systems. Emerging evidence indicate that common mechanisms regulate food and alcohol intake and raise the possibility that endocrine signals from the gut may play an important role for alcohol consumption, alcohol-induced reward and the motivation to consume alcohol. Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide regulating food intake and glucose homeostasis, has recently been shown to target central brain areas involved in reward and motivation, including the ventral tegmental area and nucleus accumbens. Herein we investigated the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on various measures of alcohol-induced reward as well as on alcohol intake and alcohol seeking behavior in rodents. Treatment with Ex4, at a dose with no effect per se, attenuated alcohol-induced locomotor stimulation and accumbal dopamine release in mice. Furthermore, conditioned place preference for alcohol was abolished by both acute and chronic treatment with Ex4 in mice. Finally we found that Ex4 treatment decreased alcohol intake, using the intermittent access 20% alcohol two-bottle-choice model, as well as alcohol seeking behavior, using the progressive ratio test in the operant self-administration model, in rats. These novel findings indicate that GLP-1 signaling attenuates the reinforcing properties of alcohol implying that the physiological role of GLP-1 extends beyond glucose homeostasis and food intake regulation. Collectively these findings implicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for alcohol use disorders.