Conventional mammalian models of anxiety with proven value for detection of the anxiolytic actions of benzodiazepines generally are unresponsive or show variable responsiveness to non-benzodiazepine anxiolytics such as buspirone. The long-term goal of the proposed research is to characterize a new, rapid, inexpensive, non-punishing, quantitative murine behavioral method with promising attributes of responsiveness to both conventional and non-conventional anxiolytic agents. The project will extend the pharmacological and behavioral characterization of a specific exploratory activity of mice, aversion to enter a mirrored chamber. This novel method is based on the approach-avoidance behavior exhibited by male animals of many vertebrate species when mirrors are placed in their immediate environment. The paradigm appears to have considerable potential value for operationally defining the actions of anxiolytics. Dosage dependent quantitative changes of large magnitude have been observed in three indices of aversion to enter a mirrored chamber (latency to enter, number of entries and time spent inside the chamber) following administration of diazepam and buspirone. These changes in behavior are not related to motor effects and will be used as endpoints in the planned experiments. A genetically defined, inbred strain of mice, BALB/cByJ, will be utilized because it is responsive to prototype anxiolytics and its genetic homogeneity should facilitate reproducibility of drug response comparisons within and between laboratories. The current study has three specific aims: 1) to establish an automated, computerized method for quantitating mirrored chamber aversive behavior in mice; 2) to determine the spectrum and specificity of pharmacological agents which acutely affect mirrored chamber aversive behavior using the computerized method developed in Aim 1; 3) to evaluate behavioral, environmental and other variables which may significantly alter intrinsic mirrored chamber aversive behavior and responsiveness to anxiolytic agents.
| Garrett, K M; Niekrasz, I; Haque, D et al. (1998) Genotypic differences between C57BL/6 and A inbred mice in anxiolytic and sedative actions of diazepam. Behav Genet 28:125-36 |
| Garrett, K M; Haque, D; Berry, D et al. (1997) The GABAA receptor alpha 6 subunit gene (Gabra6) is tightly linked to the alpha 1-gamma 2 subunit cluster on mouse chromosome 11. Brain Res Mol Brain Res 45:133-7 |
| Seale, T W; Niekrasz, I; Garrett, K M (1996) Anxiolytics by ethanol, diazepam and buspirone in a novel murine behavioral assay. Neuroreport 7:1803-8 |
