Unsignaled morphine delivery does not disrupt the development of associative morphine tolerance in the rat.
When morphine administration is paired with a distinctive context, tolerance to morphine's analgesic effects comes readily under the associative control of the drug-paired context. These associative tolerance effects are eliminated when a relatively short (i.e., 6 h) interdose interval (IDI) is used for conditioning. Contemporary models of learned tolerance explain the absence of learning at short IDIs by positing that residual morphine effects from a recent drug exposure disrupt the formation of drug-context associations. The present studies examined the impact of unsignaled morphine injections given 6 h prior to drug-context pairings on the development of associative tolerance. Analgesia was measured by the tail-flick method, and tolerance levels were assessed by dose-response curve methodology. Morphine preexposure had no detectable influence on the acquisition of associative tolerance when rats were tested immediately after conditioning, after a 30-day rest interval, or after a 30-day period of daily saline injections in their home-cage environment. These data suggest disruption of associative tolerance effects at short IDIs is not attributable to residual effects of morphine from the immediately preceding trial.
Cepeda-Benito
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Texas A&M University, Department of Psychology, College Station 77843-4235, USA.
Tiffany
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ST
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005108:Extinction, Psychological / Q000187:drug effects; D006185:Habituation, Psychophysiologic; D006234:Handling, Psychological; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
D009294:Narcotics; D009020:Morphine