Aversive and antiaversive effects of morphine in the dorsal periaqueductal gray of rats submitted to the elevated plus-maze test.

The dorsal periaqueductal gray (DPAG) is a well-known region for processing defensive behavior in the brainstem. Rats implanted with cannulae in the DPAG were submitted to the elevated plus-maze test for 5 min. The effects of morphine following systemic (0.1-1.0 mg/kg) or DPAG administration (5-30 nmol) were compared with the benzodiazepine compound midazolam injected similarly (1-10 mg/kg, IP, and 10-80 nM, DPAG). Morphine and midazolam caused dose-dependent increases in the number of entries and time spent in the open arms. A systemic injection of naloxone in doses that block mu-opioid receptors reversed the effects of centrally administered morphine. Higher doses of morphine (70 nmol) induced a non-naloxone-reversible "fearful" hyperreactivity. It is suggested that low doses of morphine inhibit the neural substrate of aversion in the DPAG, probably through activation of mu-receptors, and that microinjections of higher doses of morphine cause proaversive actions not mediated by these opioid receptors.