Pharmacological blockade of opioid receptors in the ventrolateral periaqueductal gray does not affect avoidance acquisition or performance in rats

Avoidance learning involves associating a behavioral response with the omission of an expected threat, but the neural mechanisms that drive this learning remain unclear. Research on fear extinction points to a critical role for opioid receptors in the ventrolateral periaqueductal gray (vlPAG) in computing the aversive prediction error signal that is generated when there is a difference between expected and actual aversive events. Based on these fear extinction findings, we hypothesized that vlPAG opioid signaling might also support the early stages of avoidance learning. To test this, 15 Wistar rats (7 females, 8 males) received intra-vlPAG infusions of either naloxone hydrochloride (n = 7, 2.5 g/0.5 l), a non-selective opioid receptor antagonist, or vehicle (n = 8, 0.5 l), immediately before the first and second session of two-way active avoidance training. No infusions were given before the third session, to examine avoidance performance under continued, drug-free acquisition. For the fourth and final session, drug conditions were reversed to examine the acute effect of naloxone on already established avoidance performance. Our results indicate that unilateral intra-vlPAG naloxone, at the tested dose and timing, did not significantly impair avoidance acquisition, nor its performance. These findings do not support a role for opioid signaling in the vlPAG during the initial learning or expression of two-way active avoidance.