The Evolution of Psychological and Behavioral Consequences of Self-Isolation During Lockdown: A Longitudinal Study Across United Kingdom and Italy.

Introduction: Several countries imposed nationwide or partial lockdowns to limit the spread of COVID-19 and avoid overwhelming hospitals and intensive care units. Lockdown may involve restriction of movement, stay-at-home orders and self-isolation, which may have dramatic consequences on mental health. Recent studies demonstrated that the negative impact of lockdown restrictions depends on a wide range of psychological and socio-demographic factors. Aims: This longitudinal study aimed to understand how internal factors such as personality and mindfulness traits, and external factors, such as daily habits and house features, affect anxiety, depression and general wellbeing indicators, as well as cognitive functions, during the course of a lockdown. Methods: To address these questions, 96 participants in Italy and the United Kingdom filled out a survey, once a week for 4 weeks, during the first-wave lockdowns. The survey included questions related to their habits and features of the house, as well as validated questionnaires to measure personality traits, mindful attitude and post-traumatic symptoms. Indicators of wellbeing were the affective state, anxiety, stress and psychopathological indices. We also measured the emotional impact of the pandemic on cognitive ability by using two online behavioral tasks [emotional Stroop task (EST) and visual search]. Results: We found that internal factors influenced participants' wellbeing during the first week of the study, while external factors affected participants in the last weeks. In the first week, internal variables such as openness, conscientiousness and being non-judgmental toward one's own thoughts and emotions were positively associated with wellbeing; instead, neuroticism and the tendency to observe and describe one's own thoughts and emotions had detrimental effects on wellbeing. Toward the end of the study, external variables such as watching television and movies, browsing the internet, walking the dog, and having a balcony showed a protective value, while social networking and engaging in video calls predicted lower values of wellbeing. We did not find any effects of wellbeing on cognitive functioning. Conclusion: Recognizing specific traits and habits affecting individuals' wellbeing (in both short and long terms) during social isolation is crucial to identify people at risk of developing psychological distress and help refine current guidelines to alleviate the psychological consequences of prolonged lockdowns.

Willingness of the UK public to volunteer for testing in relation to the COVID-19 pandemic.

BACKGROUND: The World Health Organization declared the rapid spread of COVID-19 around the world to be a global public health emergency. The spread of the disease is influenced by people's willingness to adopt preventative public health behaviours, such as participation in testing programmes, and risk perception can be an important determinant of engagement in such behaviours. METHODS: In this study, we present the first assessment during the first wave of the pandemic and the early stages of the first UK lockdown in April & May 2020 of how the UK public (N = 778) perceived the usefulness of testing for coronavirus and the factors that influence a person's willingness to test for coronavirus. RESULTS: None of the key demographic characteristics (age, gender, education, disability, vulnerability status, or professional expertise) were significantly related to the respondents' willingness to be tested for coronavirus. However, closely following the news media was positively related to willingness to be tested. Knowledge and perceptions about coronavirus significantly predicted willingness to test, with three significantly contributing factors: worry about the health and social impacts to self and family; personal susceptibility; and concerns about the impacts of coronavirus on specific demographic groups. Views on testing for coronavirus predicted willingness to test, with the most influential factors being importance of testing by need; negative views about widespread testing; and mistrust in doctor's advice about testing. CONCLUSIONS: Implications for effective risk communication and localised public health approaches to encouraging public to put themselves forward for testing are discussed. We strongly advocate for effective communications and localised intervention by public health authorities, using media outlets to ensure that members of the public get tested for SARs-CoV2 when required.

Knowledge, Attitude, and Practice Regarding Zoonotic Risk in Wildlife Trade, Southern China.

Current wildlife trade practices in China lead to significant interactions between humans and animals and drive the emergence of zoonotic diseases. The at-risk behaviors, knowledge, and attitudes that influence health-related behaviors in relation to animal contact and safety measures in the trade remain poorly understood. A self-administered questionnaire survey was conducted among 947 adult Internet users in three provinces in southern China to assess knowledge, perceived disease risks, at-risk behaviors, and the association of these factors with other demographic factors among the target population. Few of the participants possessed sufficient knowledge of zoonotic diseases. Although most participants were opposed to the use of wild animal resources, many reported keeping wild animals as pets (30.7%) and eating wild animals (30.5%). The majority of participants (76.3%) believed the disease transmission via wildlife trade, but few connected contact with animals to sickness (18.5%) and only slightly more than half sought post-exposure treatment (54.4%). These results reveal low levels of knowledge and perceived risk regarding disease emergence from the animal-human interactions in wildlife trade and uncover the gaps in knowledge and attitudes as key challenges to the development of health behavior change interventions pertaining to wildlife trade.

Human-animal interactions and bat coronavirus spillover potential among rural residents in Southern China.

Human interaction with animals has been implicated as a primary risk factor for several high impact zoonoses, including many bat-origin viral diseases. However the animal-to-human spillover events that lead to emerging diseases are rarely observed or clinically examined, and the link between specific interactions and spillover risk is poorly understood. To investigate this phenomenon, we conducted biological-behavioral surveillance among rural residents in Yunnan, Guangxi, and Guangdong districts of Southern China, where we have identified a number of SARS-related coronaviruses in bats. Serum samples were tested for four bat-borne coronaviruses using newly developed enzyme-linked immunosorbent assays (ELISA). Survey data were used to characterize associations between human-animal contact and bat coronavirus spillover risk. A total of 1,596 residents were enrolled in the study from 2015 to 2017. Nine participants (0.6%) tested positive for bat coronaviruses. 265 (17%) participants reported severe acute respiratory infections (SARI) and/or influenza-like illness (ILI) symptoms in the past year, which were associated with poultry, carnivore, rodent/shrew, or bat contact, with variability by family income and district of residence. This study provides serological evidence of bat coronavirus spillover in rural communities in Southern China. The low seroprevalence observed in this study suggests that bat coronavirus spillover is a rare event. Nonetheless, this study highlights associations between human-animal interaction and zoonotic spillover risk. These findings can be used to support targeted biological behavioral surveillance in high-risk geographic areas in order to reduce the risk of zoonotic disease emergence.

Problematic internet use and mental health among British children and adolescents.

Despite concerns about the effects of internet use, little is known about how problematic internet use impacts on British children and adolescents. By adapting the Problematic Internet Use Questionnaire (PIUQ, Demetrovics, Szeredi, & Rózsa, 2008), this study seeks its validation while studying its association with psychopathological and health problems. A sample of 1,814 children and adolescents (aged 10-16 years old) from UK schools completed questionnaires about PIU, behavioural problems, depression, anxiety and health problems. Confirmatory Factor Analysis identified three independent factors: Neglect, Obsession and Control Disorder. Using path analysis, PIU was significantly predicted by conduct problems, hyperactivity, impact on daily life activities, depression and poorer physical health. Males were more likely than females to score higher on PIU. The study shows for the first time that the adapted PIU questionnaire constitutes a valid tool for the assessment of problematic internet use among children/adolescents. The results also suggest an urgent need for the development of intervention strategies.

Rapid-onset anorectic effects of intranasal oxytocin in young men.

Although the neuropeptide oxytocin exhibits many of the characteristics that would support its use as an anorectic agent for overeaters, studies of oxytocin's effectiveness at reducing eating in humans remain limited. In a double-blind, placebo-controlled crossover study, under the pretext of examining oxytocin's effects on various aspects of sensory perception, 20 men were given 24 IU of oxytocin and took a taste test of sweet, salty, and neutral snacks 45 min later. Participants self-rated appetite, anxiety, and other mood parameters, and then were left alone for 10 min with the pre-weighed snack food and invited to help themselves. To minimize the influence of hunger-driven eating, lunch had been provided immediately after oxytocin administration. In line with Ott et al. (2013), oxytocin significantly reduced the consumption of sweet foods; however, it also reduced consumption of salty snacks. Self-reported anxiety did not differ across drug conditions. The study is the first to demonstrate an effect of oxytocin on snack eating at 45 min post administration and on salty snacks. The anorectic efficacy of oxytocin after 45 min cannot easily be explained by the same mechanism as the one presumed to underpin its effects in previous studies that adopted much longer intervals between drug administration and testing.

The Pregnancy Related Beliefs Questionnaire (PRBQ): An examination of the psychometric properties in perinatal samples.

BACKGROUND: Identifying vulnerability to perinatal depression is an important public health issue. Risk factors include general and maternal-specific dysfunctional attitudes. Scales of maternal attitudes have a number of shortcomings. Further, it is not known whether antenatal maternal attitudes predict post-natal depression, independently of general dysfunctional attitudes (GDA). The aim of the current study was to examine the psychometric properties of the Pregnancy Related Beliefs Questionnaire (PRBQ) and to establish, prospectively, the utility of the revised PRBQ in predicting the symptoms of post-natal depression. METHOD: In Study 1, a cross-sectional sample of 344 participants, who were either pregnant or in the post-natal period, completed a battery of questionnaires assessing background factors, GDA, attitudes specific to motherhood (PRBQ), and depression. In Study 2, a sample of 210 women completed a battery of questionnaires, including a measure of GDA, the PRBQ-8, and depression, on two occasions: early in the second trimester of pregnancy and post-natally. RESULTS: Exploratory and confirmatory factor analyses supported a one-factor, eight-item measure of maladaptive attitudes specific to motherhood (PRBQ-8). The PRBQ-8 was found to have good convergent, concurrent, and predictive validity and high internal and test-retest reliability. A hierarchical regression analysis revealed that antenatal PRBQ-8 scores predict the severity of post-natal depression symptoms, after controlling for background factors, antenatal depression, and GDA. CONCLUSIONS: The PRBQ-8 is a psychometrically sound measure of maternal attitudes that can be used antenatally to identify women at risk of post-natal depression.

Brain indices of disagreement with one's social values predict EU referendum voting behavior.

Pre-electoral surveys typically attempt, and sometimes fail, to predict voting behavior on the basis of explicit measures of agreement or disagreement with a candidate or political position. Here, we assessed whether a specific brain signature of disagreement with one's social values, the event-related potential component N400, could be predictive of voting behavior. We examined this possibility in the context of the EU referendum in the UK. In the 5 weeks preceding the referendum, we recorded the N400 while participants with different vote intentions expressed their agreement or disagreement with pro- and against-EU statements. We showed that the N400 responded to statements incongruent with one's view regarding the EU. Crucially, this effect predicted actual voting behavior in decided as well as undecided voters. The N400 was a better predictor of voting choice than an explicit index of preference based on the behavioral responses. Our findings demonstrate that well-defined patterns of brain activity can forecast future voting behavior.

One clinic's experience with carbon fiber orthoses in neuromuscular disease.

INTRODUCTION: The purpose of this study was to summarize our experience with off-the-shelf anterior shell carbon fiber ankle-foot orthoses (CFAFOs) prescribed to adult neuromuscular patients in an outpatient clinic. METHODS: We studied ambulatory patients who were seen in Muscular Dystrophy Association or amyotrophic lateral sclerosis clinics between 2011 and 2014 and prescribed anterior shell CFAFOs. Charts were reviewed with attention to diagnosis, satisfaction with use, and reasons for acceptance or rejection. We included individuals who were currently using AFOs and those being prescribed AFOs for the first time. We were especially interested in reasons for acceptance or rejection of the orthosis. RESULTS: Two hundred eighty-three charts were reviewed. Of these, 109 of 123 (89%) patients were satisfied or extremely satisfied with the anterior shell CFAFOs, including 38 who had previously used other styles. CONCLUSION: Anterior shell CFAFOs should be considered for most neuromuscular patients with distal leg weakness. Muscle Nerve 55: 202-205, 2017.

Estimates of the Absolute and Relative Strengths of Diverse Alcoholic Drinks by Young People.

BACKGROUND: Evidence suggests that college students are often unclear about how much alcohol is present in different drinks. OBJECTIVES: To evaluate the abilities of students to estimate the alcohol contents of drinks, both in relative and absolute terms, and to examine how alcohol strength informs behavior. METHODS: For 10 popular drinks that varied by alcohol content, beverage and volume, 209 UK university students rank-ordered the drinks according to total alcohol content and then estimated, for each drink, the number of UK "units" of alcohol contained and its percentage alcohol-by-volume (% ABV). Participants also reported the importance of drink strength as a factor in drink choice, and its influence in different scenarios. RESULTS: There was low but significant concordance between participants' rank-orderings of drinks by strength, and the correlation of mean ranks with correct ranks was also significant. However, their explicit estimates of the numbers of "units" in the drinks, and their % ABV values, often diverged dramatically from actual values. Participants tended to overestimate the unit contents of spirit-based drinks but underestimated the unit contents of beers and wine; women were consistently less accurate than men, typically making greater underestimates for commonly-consumed drinks. Over one-third of the sample reported that strength influenced drink choice, but its importance ranked below flavor and cost; drink strength might contribute to drink choice depending on the drinking situation. Conclusion/Importance: Young drinkers (women especially) have a poor awareness of the alcohol contents of different drinks, particularly wines and beers, but they make better judgments of relative strength.

The effects of alcohol on the recognition of facial expressions and microexpressions of emotion: enhanced recognition of disgust and contempt.

OBJECTIVE: The study compared alcohol's effects on the recognition of briefly displayed facial expressions of emotion (so-called microexpressions) with expressions presented for a longer period. METHOD: Using a repeated-measures design, we tested 18 participants three times (counterbalanced), after (i) a placebo drink, (ii) a low-to-moderate dose of alcohol (0.17 g/kg women; 0.20 g/kg men) and (iii) a moderate-to-high dose of alcohol (0.52 g/kg women; 0.60 g/kg men). On each session, participants were presented with stimuli representing six emotions (happiness, sadness, anger, fear, disgust and contempt) overlaid on a generic avatar in a six-alternative forced-choice paradigm. A neutral expression (1 s) preceded and followed a target expression presented for 200 ms (microexpressions) or 400 ms. Participants mouse clicked the correct answer. RESULTS: The recognition of disgust was significantly better after the high dose of alcohol than after the low dose or placebo drinks at both durations of stimulus presentation. A similar profile of effects was found for the recognition of contempt. There were no effects on response latencies. CONCLUSION: Alcohol can increase sensitivity to expressions of disgust and contempt. Such effects are not dependent on stimulus duration up to 400 ms and may reflect contextual modulation of alcohol's effects on emotion recognition.

Conditioned tolerance to the effects of alcohol on inhibitory control in humans.

AIMS: To test whether the repeated consumption of alcohol in a particular environment leads to the emergence of a context-specific conditioned compensatory response (CCR) that can counter alcohol's impairment of inhibitory processes. METHODS: Twenty-four participants consumed an alcoholic drink (males: 0.65 g/kg; females: 0.57 g/kg) in one context on three sessions and a matched placebo drink in a different context on three other sessions. At test, participants were split into two groups and consumed a novel alcoholic drink either in the context previously paired with alcohol or the placebo-paired context. On all sessions, participants were tested on two computer-based tasks that measured response inhibition: an affective go/no-go task and a stop-signal task (SST). RESULTS: Over the conditioning trials, tolerance developed to alcohol's disinhibitory effects on the go/no-go task; moreover, on the test for conditioned responding, performance was less impaired for participants in the alcohol-paired versus the placebo-paired context. No tolerance was evident on the SST, and no CCR. CONCLUSION: Repeated consumption of alcohol in a particular environment can lead to the emergence of a context-specific CCR that counters some of alcohol's disinhibitory effects. Therefore, consuming alcohol in an unfamiliar context might produce stronger disinhibitory effects than would be apparent in a familiar drinking environment.

Effect of cues associated with an alcoholic beverage on executive function.

OBJECTIVE: To investigate whether alcohol-associated drink cues can elicit conditioned compensatory responses that counter alcohol's effects on cognition. METHOD: A between-subjects design was used in which participants were randomly assigned to one of three drink groups: an alcohol-associated drink (lager based) or one of two drinks not usually associated with alcohol (a fruit squash-flavored drink or an apple schnapps-flavored drink; n = 15 per group). The amount of alcohol in each was the same: 0.65 g/kg body weight for men and 0.57 g/kg for women. Executive functions of inhibition, updating of working memory, and attentional set shifting were measured using the CANTABeclipse computerized test battery before and after alcohol consumption. Self-reported mood was measured, and participants provided ratings of the drinks' sensory and hedonic properties. RESULTS: Participants in the lager drink group showed less disinhibitory responding in an affective go/nogo task and less of a reduction in alertness than participants in the two other groups. The lager group was also faster to respond in the set-shifting task than the group given the "squash" (nonassociated) drink. There were no significant differences between the groups in how they evaluated the drinks' sensory/hedonic properties. CONCLUSIONS: These data provide provisional evidence to suggest that cues previously associated with alcohol in lager drinkers (particularly the taste and smell of lager) can elicit compensatory responses that counter alcohol's cognitive effects and its effects on alertness.

Conditioned effects of caffeine on performance in humans.

There is limited evidence for the conditioning of stimulant-like drug effects to previously-neutral stimuli in humans. Two studies tested whether the facilitatory effects of caffeine on cognitive performance can be conditioned to the context of drug administration. In Experiment 1, sixteen participants were divided equally into two groups: one group (the "paired" group) received 250 mg caffeine in a novel beverage prior to completing two computerized performance tests; the other group (the "unpaired" group) received the same beverage without caffeine (i.e. placebo) before testing. After the performance tests, the unpaired group received the caffeinated drink, and the paired group received placebo in a different context from that in which testing had taken place. The performance tests comprised a test of simple reaction time to a visual stimulus and a test of logical reasoning (the semantic verification task). The procedure was repeated over four separate conditioning trials. On a subsequent fifth session, the test for a conditioned response, all participants received placebo before test. Simple reaction time was significantly reduced by caffeine over the four conditioning trials, and on the test for conditioned responding the paired group performed significantly faster than the unpaired group, indicating the development of a conditioned response. In Experiment 2, twelve participants attended four conditioning trials in which either 250 mg of caffeine (two sessions) or placebo (two sessions) were paired with two visually distinct environments. After completing the conditioning sessions, tests for conditional responding were conducted by administering placebo in both contexts. During the conditioning phase, caffeine significantly improved reaction time performance relative to placebo, and this advantage was maintained at test in the CS+ context when placebo was administered in both contexts. Therefore the facilitatory effects of caffeine on performance can be elicited, in the absence of drug, by previously-neutral contextual stimuli that have been paired with drug administration.

Dissociations between motor timing, motor coordination, and time perception after the administration of alcohol or caffeine.

RATIONALE: The impacts of psychoactive drugs on timing have usefully informed theories of timing and its substrates. OBJECTIVES: The objectives of the study are to test the effects of alcohol and caffeine on the explicit timing involved in tapping with the implicit timing observed in the coordinated picking up of an object, and with the temporal discrimination. MATERIALS AND METHODS: Participants in the "alcohol" experiment (N = 16) received placebo, "low" (0.12 g/kg or 0.14 g/kg for women/men, respectively) or "high" (0.37 g/kg or 0.42 g/kg, respectively) doses of alcohol, and those in the "caffeine" experiment (N = 16) received placebo, 200 or 400 mg caffeine. Time production variability was measured by repetitive tapping of specified intervals, and sources of variance attributable to central timer processes and peripheral motor implementation were dissociated. The explicit timing in tapping was compared with the implicit timing in the coordinated picking up of an object. Time perception was measured as discrimination thresholds for intervals of similar duration. Drug effects on reaction time were also measured. RESULTS: For tapping, alcohol significantly increased timer variability, but not motor variability; it did not affect coordination timing in the grip-lift task. Conversely, for time perception, the low dose of alcohol improved temporal discrimination. Caffeine produced no effects on any of the timing tasks, despite significantly reducing reaction times. CONCLUSIONS: The effects of alcohol argue against a common clock process underlying time interval perception and production in the range below 1 s. In contrast to reaction time measures, time perception and time production appear relatively insensitive to caffeine.

Identification of guanylate cyclases and related signaling proteins in sperm tail from sea stars by mass spectrometry.

Marine invertebrates employ external fertilization to take the advantages of sexual reproduction as one of excellent survival strategies. To prevent mismatching, successful fertilization can be made only after going though strictly defined steps in the fertilization. In sea stars, the fertilization process starts with the chemotaxis of sperm followed by hyperactivation of sperm upon arriving onto the egg coat, and then sperm penetrate to the egg coat before achieving the fusion. To investigate whether the initiation of chemotaxis and the following signaling has species specificity, we conducted comparative studies in the protein level among sea stars, Asterias amurensis, A. forbesi, and Asterina pectinifera. Since transcription of messenger ribonucleic acid (mRNA) has been suppressed in gamete, the roles of sperm proteins during the fertilization cannot be investigated by examining the mRNA profile. Therefore, proteomics analysis by mass spectrometry was used in this study. In sea stars, upon receiving asteroidal sperm-activating peptide (asterosap), the receptor membrane-bound guanylate cyclases in the sperm tail trigger sperm chemotaxis. We confirmed the presence of membrane-bound guanylate cyclases in the three sea star species, and they all had the same structural domains including the extracellular domain, kinase-like domain, and guanylate cyclase domain. The majority of peptides recovered were from alpha-helices distributed on the solvent side of the protein. More peptides were recovered from the intracellular domains. The transmembrane domain has not been recovered. The functions of the receptors seemed to be conserved among the species. Furthermore, we identified proteins that may be involved in the guanylate cyclase-triggered signaling pathway.

Effects of dopamine D1-like receptor agonists on food-maintained operant behavior in rats.

The effects on learned operant behavior of agonist actions at dopamine D1-like receptors have not been fully characterized. We compared three D1-like receptor agonists (SKF 38393, SKF 77434 and SKF 82958), both alone and in combination with the D1-like receptor antagonist, SCH 23390. Binding affinities for the agonists at dopamine D1 receptors from rat striatum membranes were determined and compared with effects on behavior. Lever pressing was maintained by food reinforcement under a fixed-ratio 30-response schedule (each 30th response produced reinforcement), and the effects of the three agonists were assessed by cumulative dosing. Each drug produced dose-related reductions in response rates, with an order of potency (SKF 82958>SKF 77434>SKF 38393) that agreed with rank order of binding affinities. Antagonism of these behavioral effects by SCH 23390 was only significant for SKF 82958; surprisingly, SCH 23390 enhanced the effects of SKF 38393. For SKF 82958, the antagonism was receptor subtype-specific, as the D2-like receptor antagonist spiperone was ineffective. The nonselective serotonergic antagonist metergoline produced a significant rightward shift of the SKF 38393 dose-response function, indicating effective antagonism, although the degree of antagonism was not dose-related. These results support the view that the behavioral effects of D1-like receptor agonists differ in their susceptibility to antagonism by D1-like receptor antagonists, and that some effects of SKF 38393 may be mediated by serotonergic activity rather than by activity at D1-like receptors.

A comparison of the locomotor stimulant effects of D1-like receptor agonists in mice.

Efficacy in stimulating adenylyl cyclase (AC) has traditionally been used to distinguish dopamine D1-like receptor agonists from dopamine D2-like receptor agonists. However, there is a limited association between the effects of D1-like agonists in behavioral assays and their effectiveness at stimulating AC. Other second messenger actions might contribute to the behavioral effects of D1-like agonists, as there is evidence for a link to the hydrolysis of phosphoinositide (PI). The present study compared the locomotor stimulant effects of five D1-like receptor agonists having different efficacies in assays of AC and PI activity. All D1-like agonists produced long-lasting biphasic effects on locomotor activity. SKF 38393, the prototypical partial agonist (based on AC activity), produced limited changes in locomotor activity, whereas the partial agonists SKF 75670 and SKF 77434 produced locomotor stimulant effects that were similar to or greater than those of the full efficacy agonists SKF 82958 and SKF 81297. However, there did not appear to be a relationship between maximal behavioral effects and AC stimulation or PI hydrolysis. The results suggest a complex relationship between the behavioral effects of D1-like agonists and their intrinsic efficacies as measured by AC and /or PI stimulation. Although a limited number of compounds were examined, neither second messenger system alone appears to account fully for these behavioral effects. The current classification of D1-like agonists according to their intrinsic efficacies as defined by AC stimulation needs further scrutiny.

Genome diversification in phylogenetic lineages I and II of Listeria monocytogenes: identification of segments unique to lineage II populations.

Thirteen different serotypes of Listeria monocytogenes can be distinguished on the basis of variation in somatic and flagellar antigens. Although the known virulence genes are present in all serotypes, greater than 90% of human cases of listeriosis are caused by serotypes 1/2a, 1/2b, and 4b and nearly all outbreaks of food-borne listeriosis have been caused by serotype 4b strains. Phylogenetic analysis of these three common clinical serotypes places them into two different lineages, with serotypes 1/2b and 4b belonging to lineage I and 1/2a belonging to lineage II. To begin examining evolution of the genome in these serotypes, DNA microarray analysis was used to identify lineage-specific and serotype-specific differences in genome content. A set of 44 strains representing serotypes 1/2a, 1/2b, and 4b was probed with a shotgun DNA microarray constructed from the serotype 1/2a strain 10403s. Clones spanning 47 different genes in 16 different contiguous segments relative to the lineage II 1/2a genome were found to be absent in all lineage I strains tested (serotype 4b and 1/2b) and an additional nine were altered exclusively in 4b strains. Southern hybridization confirmed that conserved alterations were, in all but two loci, due to absence of the segments from the genome. Genes within these contiguous segments comprise five functional categories, including genes involved in synthesis of cell surface molecules and regulation of virulence gene expression. Phylogenetic reconstruction and examination of compositional bias in the regions of difference are consistent with a model in which the ancestor of the two lineages had the 1/2 somatic serotype and the regions absent in the lineage I genome arose by loss of ancestral sequences.

Dopaminergic and cholinergic involvement in the discriminative stimulus effects of nicotine and cocaine in rats.

RATIONALE: Previous work has demonstrated asymmetrical cross-generalization between the discriminative stimulus effects of nicotine and cocaine: nicotine fully substitutes for cocaine, whereas cocaine only partially substitutes for nicotine. The factors responsible for the similarities and differences between the two drugs remain unclear. OBJECTIVE: The study tested the involvement of dopaminergic and/or cholinergic mechanisms in the discriminative stimulus effects of nicotine and cocaine. METHODS: One set of rats was trained to discriminate cocaine (8.9 mg/kg) from saline, and two other sets of rats were trained to discriminate nicotine (0.1 mg/kg) from saline. RESULTS: In cocaine-trained rats, among the cholinergic agonists studied only nicotine (0.01-0.56 mg/kg) produced full, dose-related substitution; nornicotine (1-5.6 mg/kg) substituted only partially, and lobeline (2.71-15.34 mg/kg) and pilocarpine (0.26-2.55 mg/kg) failed to engender any cocaine-appropriate responding. The nicotinic antagonist mecamylamine (1-5.6 mg/kg) failed to block cocaine's discriminative stimulus effects. The dopamine antagonist cis-flupentixol (0.48 mg/kg) blocked the substitution of nicotine for cocaine. In nicotine-trained rats, the dopamine uptake blockers cocaine, bupropion and nomifensine (0.2-26.1 mg/kg) each substituted only partially for nicotine, and cis-flupentixol (0.48-0.86 mg/kg) antagonized the discriminative stimulus effects of nicotine. CONCLUSIONS: Nicotine fully substitutes for cocaine because of its effects on dopamine transmission, and not because the discriminative stimulus effects of cocaine incorporate a cholinergic component. Substitution of nicotine for cocaine may depend more on nicotine-induced dopamine release than does the nicotine-trained discriminative stimulus; there may be differential dopaminergic involvement after acute and repeated treatment with nicotine or cocaine.