Footshock- and Psychological-Stress Prevent the Development of Tolerance to Spinal but Not Supraspinal Morphine

Abstract

The site of action involved in the suppression by exposure to footshock (FS)- and psychological (PSY)-stress of the development of antinociceptive tolerance to morphine has been investigated. Daily treatment with 10 mg/kg, s.c.; 3μg, i.t.; and 5μg, i.c.v. of morphine, regardless of the administration route, resulted in the development of tolerance. Daily exposure to FS- or PSY-stress suppressed the development of tolerance to s.c. and i.t. administered morphine but not that to i.c.v. administered morphine. Pretreatment with 2 mg/kg, i.p. of nor-binaltorphimine (nor-BNI) abolished the suppressive effect of PSY-stress on the development of tolerance to morphine given s.c. The suppression by PSY-stress was also antagonized by 2μg, i.t. of nor-BNI and not by 2μg, i.c.v. of nor-BNI. Thus, the development of tolerance in the spinal cord due to interaction of morphine at μ-opioid receptors can be suppressed by exposure to these stresses, probably through the descending signals from the supraspinal area, and activation of κ-opioid receptors in the spinal cord could also participate in the suppression by PSY-stress.