The Gerbil Elevated Plus-Maze I: Behavioral Characterization and Pharmacological Validation

Several neurokinin NK1 receptor antagonists currently being developed for anxiety and depression have reduced affinity for the rat and mouse NK1 receptor compared with human. Consequently, it has proven difficult to test these agents in traditional rat and mouse models of anxiety and depression. This issue has been overcome, in part, by using non-traditional lab species such as the guinea pig and gerbil, which have NK1 receptors closer in homology to human NK1 receptors. However, there are very few reports describing the behavior of gerbils in traditional models of anxiety. The aim of the present study was to determine if the elevated plus-maze, a commonly used anxiety model, could be adapted for the gerbil. Using a specially-designed elevated plus-maze, gerbils exhibited an ‘anxious’ behavioral profile similar to that observed in rats and mice, i.e., reduced entries into, and time spent exploring, an open, aversive arm. The anxiolytic drugs diazepam (0.03–3 mg/kg i.p.), chlordiazepoxide (0.3–10 mg/kg i.p.), and buspirone (0.3–30 mg/kg s.c.) increased open arm exploration and produced anxiolytic-like effects on risk-assessment behaviors (reduced stretch-attend postures and increased head dips). Of particular interest, the antidepressant drugs imipramine (1–30 mg/kg p.o.), fluoxetine (1–30 mg/kg, p.o.) and paroxetine (0.3–10 mg/kg p.o.) each produced some acute anxiolytic-like activity, without affecting locomotor activity. The antipsychotic, haloperidol, and the psychostimulant, amphetamine, did not produce any anxiolytic-like effects (1–10 mg/kg s.c). The anxiogenic β-carboline, FG-7142, reduced time spent in the open arm and head dips, and increased stretch-attend postures (1–30 mg/kg, i.p.). These studies have demonstrated that gerbils exhibit an anxiety–like profile on an elevated plus-maze, and that the gerbil elevated plus-maze may have predictive validity for anxiolytics, and antidepressants with potential anxiolytic-like effects.