Anxiolytic-like effects of AP7 injected into the dorsolateral or ventrolateral columns of the periaqueductal gray of rats

Abstract.

Rationale: Glutamate antagonists microinjected into the dorsolateral PAG (DLPAG) show an anxiolytic-like profile in the elevated plus maze. Other columns of the PAG are also involved in defensive reactions. Few studies, however, have investigated the effects of pharmacological manipulation of the ventrolateral PAG (VLPAG) on procedures that predict anxiolytic activity. Objectives: To investigate the effects of the NMDA receptor (NMDAr) antagonist 2-amino-7-phosphonoheptanoic acid (AP7) microinjected into the DL or VLPAG in two procedures that predict anxiolytic activity using distinct aversive contingencies, the elevated plus maze and the Vogel punished licking test. Methods: Male Wistar rats (7–14/group) with cannulas aimed at the DLPAG or VLPAG received AP7 (2 nmol/0.5 µl) or saline and 10 min later were submitted to the behavioural tests. In the punished licking experiment, water deprived (48 h) animals were allowed to drink for 3 min, receiving a 0.5 mA shock every 20 licks. The elevated plus maze test was performed as described elsewhere. Using this test, a dose response-curve for AP7 (0.2–20 nmol) injected in a smaller volume (0.25 µl) into the VLPAG was also performed. Results: AP7 increased exploration of open arms of the EPM when microinjected into either the DLPAG or VLPAG (P<0.05, ANOVA). The drug also increased the number of punished licks when administered into those columns (ANOVA, P<0.05). Conclusions: The results suggest that antagonism of endogenous excitatory amino acid neurotransmission in the DLPAG or VLPAG is able to reverse behavioral suppression induced by distinct aversive contingencies.