Search

Rationale: Triangulation of approaches (i.e., using several tests of the same construct) can be extremely useful for increasing the robustness of the findings being widely used when working with behavioral testing, especially when using rodents as a translational model. Although zebrafish are widely used in neuropharmacology research due to their high-throughput screening potential for new therapeutic drugs, behavioral test battery effects following pharmacological manipulations are still unknown., Methods: Here, we tested the effects of an anxiety test battery and test time following pharmacological manipulations in zebrafish by using two behavioral tasks: the novel tank diving task (NTT) and the light-dark test (LDT). Fluoxetine and conspecific alarm substance (CAS) were chosen to induce anxiolytic and anxiogenic-like behavior, respectively., Results: For non-drug-treated animals, no differences were observed for testing order (NTT → LDT or LDT → NTT) and there was a strong correlation between performances on the two behavioral tasks. However, we found that during drug treatment, NTT/LDT responses are affected by the tested order depending on the test time being fluoxetine effects higher at the second behavioral task (6 min later) and CAS effects lower across time., Conclusions: Overall, our data supports the use of baseline behavior assessment using this anxiety test battery. However, when working with drug exposure, data analysis must carefully consider time-drug-response and data variability across behavioral tasks., (© 2021. The Author(s).)

Background: Zebrafish are growing in use as a model for understanding drug dependence and addiction. Sensitization paradigms have been a useful tool in identifying mechanisms involved in drug-induced behavioral and neurological changes, but in zebrafish have tended to focus on locomotor, rather than cognitive, endpoints., Methods: Here, we used a novel method, the FMP Y-maze, which measures continuous performance through a series of repeated binary choices (L vs R), to establish a model for assessing parameters associated with psychostimulant-induced behavioral and cognitive sensitization in adult zebrafish., Results: Repeat, intermittent exposure to d-amphetamine (AMPH) for 14 days increased alternations (LRLR) in the maze, suggesting improved working memory, which was enhanced further following drug challenge after a short withdrawal period, suggesting behavioral sensitization. However, this cognitive enhancement coincided with a reduction in the use of other exploration strategies, hypolocomotion, and inhibition of cognitive flexibility. Like AMPH, exposure to nicotine (NIC) increased alternations following drug challenge after chronic treatment. Repeat NIC exposure appeared to induce both cognitive and psychomotor sensitization, as evidenced by increased working memory performance (alternations) and locomotor activity, without negatively impacting other search strategies or cognitive flexibility., Conclusion: Chronic treatment with AMPH or NIC boosts cognitive performance in adult zebrafish. Cognitive sensitization occurred with both drugs, resulting in enhanced working memory; however, repeat AMPH exposure, following a withdrawal period, resulted in inhibited cognitive flexibility, an effect not evident with repeat NIC exposure. Cognitive and behavioral sensitization paradigms in zebrafish could serve as a useful tool for assessing cognitive states which result in cognitive enhancing or impairing effects of drugs., (© 2021. The Author(s).)

Taurine (TAU) is a β-amino sulfonic acid with pleiotropic roles in the brain, including the neuromodulatory activity via GABAergic and glycinergic agonism. This molecule is found at high concentrations in energy drinks and is often mixed with alcohol in beverages. Although TAU has a neuroprotective role in the brain, the putative risks of mixing TAU and EtOH are not fully understood. Here, we investigated whether TAU modulates locomotor and anxiety-like behavior in adult zebrafish by using the novel tank and light-dark tests following acute EtOH exposure at anxiogenic and anxiolytic concentrations. Zebrafish were individually exposed to water (control), TAU (42, 150, and 400 mg/L), and EtOH (0.25% (v/v) and 1% (v/v)) both independently and cotreated for 1 h. EtOH 0.25% and TAU produced U-shape anxiolytic-like behavior in the light-dark test, TAU 42 and 400 positively modulated EtOH effects, and TAU 150 exerted a protective effect. All TAU concentrations counteracted EtOH 1%-induced locomotion impairment, as well as the anxiogenic-like behavior. Finally, all TAU concentrations when given independently or cotreated with EtOH 0.25% and 1% decreased the risk assessment of the lit compartment. Principal component analyses revealed that exploration and anxiety-like responses were the main behaviors that contribute to the effects of TAU and EtOH. Overall, we demonstrate that TAU differently modulates EtOH-induced anxiolytic- and anxiogenic-like behaviors depending on the concentration, suggesting a complex mechanism underlying TAU and EtOH interactions.

Rationale: Chronic alcohol misuse can escalate into alcohol use disorder (AUD). The causal mechanisms through which recreational social drinking develops into compulsive uncontrolled alcohol misuse are multifaceted. For example, stress is an important risk factor that influences alcohol craving in both healthy and addicted individuals. In addition, those that are high in impulsivity/risk taking drink more and are at greater risk of developing addiction. At present, however, it is not possible accurately to predict those at risk of escalation in alcohol use, or of developing AUD., Objectives: The aim of this study was to investigate how underlying physiological and personality traits affect stress-induced craving for, and consumption of, alcohol, in a sample of social drinkers. The primary hypothesis was that impulsivity/risk-taking would modulate stress-induced alcohol craving and consumption., Methods: Thirty-nine participants (22 male and 17 female; mean age = 23.92 years [SD = 4.90]) were randomly allocated to 'stress' and 'no-stress' groups; in the stress group, participants took part in the Trier Social Stress Test (TSST). Participants completed several questionnaires and computer tasks in order to assess prior alcohol use, impulsivity/risk-taking, stress-reactivity, craving and physiological biomarkers of stress. Finally, participants completed a voluntary drinking task, in which increasing numbers of presses on a computer keyboard were reinforced with 5-ml shots of 37% ABV vodka (plus mixer)., Results: Participants exposed to the TSST showed an increase in craving following the stressor. Several factors predicted voluntary drinking, including risky decision making, slow HR recovery from stress, poor vagal tone during recovery from stress and greater stress reactivity. Surprisingly, we found no correlation between craving and consumption., Conclusions: Our data suggest that variation in physiological stress parameters and poor decision-making abilities increase risk of stress-induced alcohol consumption. This may provide a useful translational framework through which we can further study early predictive markers for the shift between controlled recreational drinking to uncontrolled alcohol misuse, including AUD.

Deficits in impulse control are related to a number of psychiatric diagnoses, including attention deficit hyperactivity disorder, addiction, and pathological gambling. Despite increases in our knowledge about the underlying neurochemical and neuroanatomical correlates, understanding of the molecular and cellular mechanisms is less well established. Understanding these mechanisms is essential in order to move towards individualized treatment programs and increase efficacy of interventions. Zebrafish are a very useful vertebrate model for exploring molecular processes underlying disease owing to their small size and genetic tractability. Their utility in terms of behavioral neuroscience, however, hinges on the validation and publication of reliable assays with adequate translational relevance. Here, we report an initial pharmacological validation of a fully automated zebrafish version of the commonly used five-choice serial reaction time task using a variable interval pre-stimulus interval. We found that atomoxetine reduced anticipatory responses (0.6 mg/kg), whereas a high-dose (4 mg/kg) methylphenidate increased anticipatory responses and the number of trials completed in a session. On the basis of these results, we argue that similar neurochemical processes in fish as in mammals may control impulsivity, as operationally defined by anticipatory responses on a continuous performance task such as this, making zebrafish potentially a good model for exploring the molecular basis of impulse control disorders and for first-round drug screening.