Involvement of dorsolateral periaqueductal gray N-methyl-D-aspartic acid glutamate receptors in the regulation of risk assessment and inhibitory avoidance behaviors in the rat elevated T-maze.

The involvement of the dorsolateral periaqueductal gray in the regulation of fear-related behaviors such as escape and freezing is well established. It is still a matter of investigation, however, whether this midbrain area may have a relevant role in the modulation of more subtle defensive responses associated with anxiety such as risk assessment and inhibitory avoidance. By stimulating N-methyl-D-aspartic acid glutamate receptors located in the dorsolateral periaqueductal gray with its prototypical agonist N-methyl-D-aspartic acid (50 pmol), we report here an increase in both risk assessment and inhibitory avoidance behaviors of male Wistar rats tested in the elevated T-maze. These results are indicative of an anxiogenic-like effect. The selective N-methyl-D-aspartic acid receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (2.0 and 4.0 nmol) had the opposite effect on both defensive tasks. Pretreatment with an ineffective dose of DL-2-amino-7-phosphonoheptanoic acid (1.0 nmol) prevented the N-methyl-D-aspartic acid anxiogenic-like effect. At the dose range of DL-2-amino-7-phosphonoheptanoic acid and/or N-methyl-D-aspartic acid tested, neither the escape response from one of the elevated T-maze open arms nor the general exploratory activity as assessed in the open-field test was affected. The present results suggest that the dorsolateral periaqueductal gray column is also involved in the regulation of defensive behaviors related to anxiety, and N-methyl-D-aspartic acid glutamate receptors are recruited for this action.