Effects of microinjections of mu and kappa receptor agonists into the dorsal periaqueductal gray of rats submitted to the plus maze test.

Several lines of evidence have shown that aversive states are under the influence of opioid mechanisms in the dorsal periaqueductal gray (DPAG). In order to characterize the type of opioid receptors involved in these effects in this work we injected DAMGO and U50,488H, mu and kappa selective agonists, respectively, directly in this structure. Rats implanted with chemitrode in the DPAG were submitted to the elevated plus maze test for 5 min. The effects of DAMGO (0.1-1 nmol/0.2 microliter) and U50,488H (1-10 nmol/0.2 microliter) following administration into DPAG were studied. Low doses of DAMGO (0.1 and 0.3 nmol) caused dose-dependent increases in the number of entries and time spent in the open arms while an overall deficit in the exploratory activity was produced by the higher dose used (1.0 nmol). Clear aversive effects were observed following the administration of U50,488H in the DPAG. The antiaversive effects of 0.3 nmol DAMGO were inhibited by the intraperitoneal administration of the mu receptor antagonist naltrexone (2.0 mg/kg, IP) whereas the aversive effects of 5.0 nmol U50,488H were antagonized by the selective kappa receptor antagonist nor-binaltorphimine (1.0 mg/kg, IP). It is suggested that activation of mu receptors inhibit and kappa receptors enhance the neural substrate of aversion in the DPAG.