Modulation of appetitively and aversively motivated behavior by the kappa opioid antagonist MR2266.

MR2266 (MR), an opioid antagonist that binds to kappa and mu receptors, was examined for its ability to influence the aversively motivated behaviors conditioned by electric shock and the drinking induced by water deprivation or the availability of a palatable saccharin/glucose solution. The intraperitoneal (ip) and intracerebroventricular (icv) administration routes were contrasted. After both ip and icv administration, MR was able to reverse conditional analgesia as measured by the formalin test. MR enhanced the Pavlovian conditional freezing response when administered icv prior to shock exposure but reduced freezing if given ip prior to shock. A related benzomorphan-derived opioid antagonist, MR1452, also reduced freezing when given ip prior to shock. MR2266 was a potent antidipsogenic agent when administered ip but had no such effect when administered icv. It is concluded that separable opioid systems are involved in the modulation of appetitively and aversively motivated behaviors.