Anxiolytic-like effects produced by bilateral lesion of the periaqueductal gray in mice: Influence of concurrent nociceptive stimulation

Threatening situations (e.g., exposure to an elevated plus-maze with four open arms – oEPM) induce behavioral and neurovegetative responses generally accompanied by antinociception in animals. The midbrain periaqueductal gray (PAG) is longitudinally divided into four columns (dorsomedial, dorsolateral, lateral and ventrolateral) that are involved in co-ordinating distinct strategies for coping with different types of stress, threat and pain. The present study evaluated the effect of unilateral or bilateral lesion of dorsal portion of PAG (dPAG: dorsolateral and dorsomedial columns) (i) on nociceptive response induced by 2.5% formalin injection into the right hind paw (nociception test) in mice exposed to a non-aversive situation or to the oEPM and (ii) on anxiety indices in mice exposed to a standard elevated plus-maze (sEPM: two open and two closed arms) with or without prior injection of 2.5% formalin. Results showed that neither pain response in a non-aversive situation (i.e. no exposure to the EPM) nor oEPM-induced antinociception were prevented by uni or bilateral lesion of dPAG. However, bilateral dPAG lesion reduced anxiety indices (% open arm entries and % open arm time) only in mice that had not received prior injection of formalin. These results suggest that either tonic pain, induced by formalin injection or oEPM-induced antinociception, do not recruit the dorsal portion of this midbrain structure. Nevertheless, the role of the ventrolateral portion of the PAG in the modulation of the nociceptive response remains undetermined. Intriguingly, concurrent nociception test impaired the antianxiety effects of bilateral lesion of dPAG. We suggest that pain stimulus has somehow impaired the anxiolytic effect of the dPAG bilateral lesion.