title: Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the rat.
abstract: The spinal cord contains endogenous substances (such as cholecystokinin, FMRFamide, etc.) that can block the analgesic effects of opiates. Anti-opiate actions have been most commonly studied by exogenous administration of receptor agonists and receptor antagonists of these substances. However, we have recently demonstrated that anti-analgesia can be brought under environmental control through Pavlovian conditioning. Whereas analgesia can be conditioned to signals for danger, anti-analgesia can be conditioned to signals for safety. Using this paradigm, we have previously demonstrated that conditioned anti-analgesia can reverse a variety of opiate analgesic states, including those produced by conditioned danger signals, systemic morphine, and intrathecal mu- and delta-opiate receptor agonists. These data raise the question of the generality of anti-analgesia actions. The present series of experiments examined the ability of conditioned anti-analgesia to affect non-opiate analgesic states induced by spinal delivery of GABA(A), GABA(B), 5HT2 + 5HT1, and 5HT3 receptor agonists. While conditioned anti-analgesia had no effect on GABA(A) or 5HT2 + 5HT1 non-opiate analgesias, conditioned anti-analgesia completely blocked GABA(B) and 5HT3 non-opiate analgesias. These findings clearly demonstrate that conditioned anti-analgesia can powerfully modulate non-opiate as well as opiate analgesias and bring into question whether putative anti-opiate neuroactive substances may have broader actions than previously suggested.
authors.affiliation: Department of Psychology, University of Colorado at Boulder, 80309, USA. lwatkins@clipr.colorado.edu
authors.forename: L R
authors.initials: LR
authors.lastname: Watkins
authors.forename: M
authors.initials: M
authors.lastname: McGorry
authors.forename: B
authors.initials: B
authors.lastname: Schwartz
authors.forename: D
authors.initials: D
authors.lastname: Sisk
authors.forename: E P
authors.initials: EP
authors.lastname: Wiertelak
authors.forename: S F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D015360:Analgesia, Epidural; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D003214:Conditioning, Classical; D004353:Drug Evaluation, Preclinical; D018755:GABA Agonists / Q000494:pharmacology; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D001645:Biguanides; D018755:GABA Agonists; D007539:Isonicotinic Acids; D009292:Narcotic Antagonists; D017366:Serotonin Receptor Agonists; D009271:Naltrexone; D001418:Baclofen; C008846:phenyl biguanide; C015300:isoguvacine