Ethopharmacological analysis of the effects of putative 'anxiogenic' agents in the mouse elevated plus-maze

The literature on the effects of anxiety-provoking agents in humans and animals is replete with inconsistent and contradictory findings as well as data that may have alternate explanations. To further our understanding in this area, ethological methods were used to assess in detail the effects of four putative anxiogenic agents in the murine elevated plus-maze test. Compounds studied were FG 7142 (1.25-10.0 mg/kg), pentylenetetrazol (PTZ; 1.875-30.0 mg/kg), isoproterenol (0.125-1.0 mg/kg), and sodium lactate (32.75-262.0 mg/kg). FG 7142 produced an anxiogenic-like profile at 10 mg/kg, an effect that could not be attributed to seizure activity or nonspecific behavioural suppression. PTZ exerted biphasic effects, with low doses (1.875-3.75 mg/kg) producing anxiolytic-like effects and high doses (20.0-30.0 mg/kg) anxiogenic-like effects. With the exception of the highest dose tested, which radically disrupted behavior, these effects of PTZ were also seen to be behaviorally specific. Although some minor behavioural changes were evident with sodium lactate and isoproterenol, neither compound altered anxiety-related measures under present test conditions. Data are discussed in relation to distinctions between anxiety and panic, and the nature of anxiety expressed in and detected by animal models.