6-methyl-2-(phenylethynyl)pyridine and Obsessive-Compulsive-Disorder

The marble burying test is used to measure repetitive and anxiety-related behaviour in rodents. The number of marbles that animals bury are count data (non-negative integers), which are bounded below by zero and above by the number of marbles present. Count data are often analysed using normal linear models, which include the t-test and analysis of variance (ANOVA) as special cases. Linear models assume that the data are unbounded and that the variance is constant across groups. These requirements are rarely met with count data, leading to 95% confidence intervals that include impossible values (less than zero or greater than the number of marbles present), misleading p-values, and impossible predictions. Transforming the data or using nonparametric methods are common alternatives but transformations do not perform well when many zero values are present and nonparametric methods have several drawbacks.. The problems with using normal linear models to analyse marble burying data are demonstrated and generalised linear models (GLMs) are introduced as more appropriate alternatives.. GLMs have been specifically developed to deal with count and other types of non-Gaussian data, are straightforward to use and interpret, and will lead to more sensible inferences.

Topics: Analysis of Variance; Animals; Anxiety; Autistic Disorder; Behavior, Animal; Calcium Carbonate; Disease Models, Animal; Linear Models; Mice; Obsessive-Compulsive Disorder; Pyridines; Statistical Distributions; Valproic Acid

Over the last decades, the inhibition of spontaneous burying of glass marbles by mice has been used as an index of anxiolytic drug action in the so-called marble burying test. Indeed, acute administration of rapid-onset (e.g. diazepam) and slow-onset (e.g. fluoxetine) anxiolytics inhibit marble burying. However, non-anxiolytic compounds such as classical antipsychotics also reduce marble burying thus suggesting that the predictive validity of this procedure for anxiety may be limited. In the present study, after having selected a strain of mice (C57BL/6J) that showed spontaneous avoidance of glass marbles, we tried to improve the predictive validity of the marble burying test for anxiety by measuring locomotor activity during the marble burying test and--if needed--in control experiments by using a videotracking system. Twenty-four reference compounds were tested including anxiolytics, anxiogenics, antidepressants, antipsychotics and other classes. By comparing marble burying scores with locomotor measures, we found that, based on our criteria, most of the anxiolytics and antidepressants selectively inhibited marble burying in contrast to most of the other compounds (e.g. haloperidol, morphine). Two putative anxiolytics, i.e. the nociceptin orphanin FQ peptide receptor agonist Ro 64-6198 and the metabotropic glutamate 5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine, also showed a selective profile. We propose this modified procedure, requiring only a limited number of animals, as a valuable screening test for the detection of compounds having anxiolytic effects.

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Behavior, Animal; Diazepam; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fluoxetine; Haloperidol; Imidazoles; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Morphine; Motor Activity; Obsessive-Compulsive Disorder; Pyridines; Reproducibility of Results; Species Specificity; Spiro Compounds