Blockade of μ- and activation of κ-opioid receptors in the dorsal periaqueductal gray matter produce defensive behavior in rats tested in the elevated plus-maze

We studied the effects of morphine injected into the dorsal periaqueductal gray using conventional and novel ethological measures of the behavior of rats submitted to the elevated plus-maze test. Morphine (20 and 40 nmol) applied into the dorsal periaqueductal gray produced dose dependent aversive effects with reduced entries and time spent in the open arms. Freezing behavior was the most prominent novel ethological measure produced by microinjections of these doses of morphine. These pro-aversive effects were not inhibited by previous dorsal periaqueductal gray microinjection of [n-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2)](CTOP) (1 nmol), a selective peptide antagonist for mu-opioid receptors. On one hand, microinjection of CTOP produced a dose dependent increase in scanning and stretched attended postures, by its own. On the other hand, the aversive effects of morphine into the dorsal periaqueductal gray microinjections were significantly reduced by systemic administration of nor-binaltorphimine, an opioid receptor antagonist with a tardive and selective action at kappa-opioid receptors. These findings suggest that mechanisms mediated by mu-opioid receptors in the dorsal periaqueductal gray may be involved in the control of risk assessment behavior. On the other hand, the pro-aversive effects produced by microinjections of morphine into the dorsal periaqueductal gray are probably mediated by kappa-opioid receptors. (C) 2000 Elsevier Science B.V. All rights reserved.