Revisiting the role of anxiety in the initial acquisition of two-way active avoidance: pharmacological, behavioural and neuroanatomical convergence

Abstract

Two-way active avoidance (TWAA) acquisition constitutes a particular case of approach -avoidance conflict for laboratory rodents. The present article reviews behavioural, psychopharmacological and neuroanatomical evidence accumulated along more than fifty years that provides strong support to the contention that anxiety is critical in the transition from CS (conditioned stimulus)-induced freezing to escape/avoidance responses during the initial stages of TWAA acquisition. Thus, anxiolytic drugs of different types accelerate avoidance acquisition, anxiogenic drugs impair it, and avoidance during these initial acquisition stages is negatively associated with other typical measures of anxiety. In addition behavioural and developmental treatments that reduce or increase anxiety/stress respectively facilitate or impair TWAA acquisition. Finally, evidence for the regulation of TWAA acquisition by septo-hippocampal and amygdala-related mechanisms is discussed. Collectively, the reviewed evidence gives support to the initial acquisition of TWAA as a paradigm with considerable predictive and (in particular) construct validity as an approach-avoidance conflict-based rodent anxiety model.

Keywords: active avoidance; amygdala circuitry; anxiety; anxiogenic treatments; anxiolytic treatments; fear; freezing; septo-hippocampal system; two-way avoidance acquisition.