Sex-independent recruitment of the dorsal periaqueductal gray in fear memory expression, consolidation, and pronounced anxiety-like state.

The dorsolateral column of the periaqueductal gray (dPAG) is a midbrain structure involved in innate defensive reactions but also contributes to processes relevant to the neurobiology of post-traumatic stress disorder (PTSD). However, whether dPAG activity contributes to the expression and consolidation of aversive memories, as well as persistent anxiety-like states, remains unclear. The present study investigated these processes in male and female Wistar rats using the conditioned place aversion (CPA) paradigm followed by the elevated plus maze (EPM) test to assess anxiety-like behavior. Chemical stimulation of the dPAG with N-methyl-D-aspartate (NMDA) served as the unconditioned stimulus, whereas functional inactivation was achieved by microinjection of cobalt chloride (CoCl2), a non-specific synaptic blocker. Inactivation was performed 1 h before the CPA test to evaluate memory expression or 1 h before the EPM test to assess anxiety-like state. In a separate experiment, the protein synthesis inhibitor anisomycin (ANS) was administered into the dPAG after conditioning to examine memory consolidation. NMDA stimulation induced robust CPA and increased anxiety-like behavior. Inactivation of the dPAG before the CPA test impaired CPA expression without altering the anxiety-like phenotype in the EPM. In contrast, inactivation before EPM exposure prevented this anxiety-like response. ANS administration impaired CPA consolidation and prevented the anxiety-like phenotype. These findings implicate the dPAG from male and female rats as a key brain area involved in the expression and consolidation of aversive memories, as well as in the development of anxiety-like states, at least when it is recruited during the aversive event.