Studies have been carried out to clarify the possible mechanism underlined in the blockade of the development of tolerance to morphine antinociception by concurrent exposure to footshock (FS) or Psychological (PSY) stress.
1. The main site of action involved in the suppression was investigated. Concomitant stresk or U-50, 488H resulted in the suppression of tolerance to intrathecal (i. t.) morphine ; however, such treatment failed to suppress the development of tolerance to intracerebroventricular (i. c. v.) morphine. Norbinaltorphimine abolished the suppression by PSY stress and U-50, 488H but not that by FS stress. Thus, these stresses suppress the development of morphine tolerance by acting on the spinal cord, and also that K-opioid receptor mechanisms could be involved in the suppression in case of PSY stress. 2. Tolerance to a drug is an adaptive response and learning and memory processes essentially endowed functions in the adaptation to environmental changes and exposure to drugs
. Thus, the role of arginine vasopressin (AVP) in the suppression by stresses was examined. Radioimmunoassayable AVP content was decreased in mouse brain hypothalamus after FS and PSY stresses. In contrast, SW stress did not affect the level. Since the exposure to stress lowing AVP levels suppress the development of tolerance, AVP may play a critical role in this mechanism. The development of tolerance to morphine was prevented by pretreatment with V_1 receptor antagonist and likewise with V_2 receptor antagonist, i. c. v. 3. FS and PSY stress failed to block the development of tolerance to clonidine, whilst SW stress resulted in the suppression of clonidine tolerance. 4. Diazepam and buspirone abolished the suppression of the development of morphine tolerance by PSY stress, and Panax ginseng extracts abolished the blockade by FS stress. To assess the abolishment of suppression by stresses may provide a simple and new screening method for the evaluation of compounds possessing antianxiety or anti-stress properties. Less