title: Decreases in nestlet shredding of mice by serotonin uptake inhibitors: comparison with marble burying.
abstract: Methods for detection of anxiolytic-like behavioral effects of serotonin uptake inhibitors are limited. The present study introduces a new quantitative method that permits dose-effect analysis of these compounds. Male NIH Swiss mice were given 60-min access to a piece of cotton gauze and the amount of material not torn into nesting material was weighed. Other groups of mice were individually placed in containers with 20 marbles resting on top of sawdust bedding. The number of marbles buried (2/3) by sawdust after 30 min was counted. Mice were first placed on a 6-rpm rotorod and the number of mice falling off twice in 2 min was measured. Serotonin uptake inhibitors (clomipramine, citalopram, fluoxetine, and venlafaxine) dose-dependently suppressed nestlet shredding and marble burying at doses that were generally without effect on rotorod performance. The amine-based antidepressant agents imipramine and desipramine as well as the selective norepinephrine transport inhibitor nisoxetine produced similar qualitative effects on these behaviors. Anxiolytics (chlordiazepoxide, bretazenil, buspirone, and pentobarbital) produced effects in the nestlet assay that were similar to those reported using another anxiolytic assay in mice (punished responding), whereas these compounds were not active at non-motor-impairing doses in the marble burying assay. The antipsychotic agents chlorpromazine and risperidone generally demonstrated suppression of nestlet shredding and marble burying at doses that impaired rotorod performance. Although d-amphetamine suppressed nestlet shredding and marble burying at doses without effect on the rotorod, d-amphetamine but not fluoxetine stimulated locomotor activity. Both nestlet shredding and marble burying behaviors were generally consistent across five consecutive experimental sessions and fluoxetine did not produce any systematic trends over repeated testing. The methods should have utility in defining pharmacological effects of these compounds in vivo. Moreover, these data may be useful in the context of other behavioral effects when assessing the relevance of a compound for its potential therapeutic potential as an anxiolytic (nestlet shredding) or as an anti-obsessive-compulsive disorder agent (marble burying).
authors.affiliation: Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-0510, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Denise
authors.initials: D
authors.lastname: Morrow
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Witkin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009425:Nesting Behavior / Q000187:drug effects* / Q000502:physiology; D009770:Obsessive Behavior / Q000188:drug therapy* / Q000523:psychology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D004856:Postural Balance / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors