Pharmacological and genetic influences on hole-board behaviors in mice

Head dipping on a hole-board is frequently used as an indicator of exploratory tendencies in rodent studies. Drugs with diverse pharmacological properties alter head dipping suggesting that many neurotransmitter systems are involved in the expression of exploratory behavior. The aim of the current experiments was to determine the effects of several drugs from different classes on head dipping, and to compare the effects of some of these agents in lines of mice that have been selectively bred for divergent expression of head dipping on a hole-board. In the current experiments, the effects on head dipping of three doses each of fluoxetine, desipramine, GBR-12909, methamphetamine, pentylenetetrazol, and diazepam were evaluated in genetically heterogeneous mice. Most drugs altered the number of head dips in a predictable manner, but the effects on locomotion were generally as large as those seen for head dipping. Locomotion could completely account for the effects of fluoxetine and pentylenetetrazol, and to a lesser extent, diazepam. We have also developed replicate lines of mice selectively bred for high (High Exploratory Behavior: HEB) or low (Low Exploratory Behavior: LEB) head dipping on a hole-board and evaluated the effects of diazepam and methamphetamine on hole-board behaviors in these mice. Diazepam increased head dipping and locomotion equivalently in both lines of mice, but methamphetamine stimulated locomotion in HEB mice more than in LEB mice. These results broadly suggest that the effects of most drugs we tested are not specific for head dipping, since almost all drugs tested affected head dipping and locomotion equivalently. However, the results with the genetically heterogeneous mice and HEB and LEB mice suggest that some aspects of the dopaminergic system are involved in head dipping. (c) 2006 Elsevier Inc. All rights reserved.