A locus and mechanism of action for associative morphine tolerance.
Repeated administration of an opioid in the presence of specific environmental cues can induce tolerance specific to that setting (associative tolerance). Prolonged or repeated administration of an opioid without consistent contextual pairing yields non-associative tolerance. Here we demonstrate that cholecystokinin acting at the cholecystokinin-B receptor is required for associative but not non-associative morphine tolerance. Morphine given in the morphine-associated context increased Fos-like immunoreactivity in the lateral amygdala and hippocampal area CA1. Microinjection of the cholecystokinin B antagonist L-365,260 into the amygdala blocked associative tolerance. These results indicate that cholecystokinin acting in the amygdala is necessary for associative tolerance to morphine's analgesic effect.
Mitchell
J M
JM
Department of Physiology, University of California, San Francisco, San Francisco, California 94143-0444, USA.
Basbaum
A I
AI
Fields
H L
HL
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001570:Benzodiazepinones / Q000008:administration & dosage; D020109:Devazepide / Q000494:pharmacology; D004361:Drug Tolerance / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010671:Phenylurea Compounds / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D009294:Narcotics; D016761:Oncogene Proteins v-fos; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D009020:Morphine; D020109:Devazepide