Year: 2002
Type: dissertation
Study designs: Systematic Review, Meta-Analysis
Abstract: From repeated administration, morphine tolerance develops when higher morphine doses are required to produce the same effect as the initial dose.Tolerance arises from two different mechanisms.The non-associative tolerance mechanism is tolerance due to compensatory responses elicited from morphine itself.The associative mechanism is tolerance due to compensatory responses elicited by distinctive cues associated with the morphine effect.Researchers usually use a paired-unpaired design with rats and morphine when studying associative tolerance.During tolerance acquisition, the DC group of rats is given morphine injections paired with distinctive cues during training and the HC group of rats is given the same number of morphine injections in their home cage.During the tolerance testing phase, both groups are given a morphine injection in the presence of the distinctive cue, and tested for analgesic tolerance.Since both groups received the same amount and number of morphine injections, the two groups should acquire the same amount of non-associative tolerance.Only the DC group, however, may acquire greater overall tolerance due to associative tolerance.According to previous studies, associative tolerance may be explained in terms of classical conditioning.The purpose of this meta-analysis was to determine if associative tolerance exists and to identify which variables may significantly moderate the acquisition of associative tolerance.Effect sizes (d) were calculated for 27 studies and study variables were coded.The DC group acquired greater tolerance vi ABSTRACT From repeated administration, morphine tolerance develops when higher morphine doses are required to produce the same effect as the initial dose.Tolerance arises Rom two different mechanisms.The non-associative tolerance mechanism is tolerance due to compensatory responses elicited from morphine itself.The associative mechanism is tolerance due to compensatory responses elicited by distinctive cues associated with the morphine effect.Researchers usually use a paired-unpaired design with rats and morphine when studying associative tolerance.During tolerance acquisition, the DC group of rats is given morphine injections paired with distinctive cues during training and the HC group of rats is given the same number of morphine injections in their home cage.During the tolerance testing phase, both groups are given a morphine injection in the presence of the distinctive cue, and tested for analgesic tolerance.Since both groups received the same amount and number of morphine injections, the two groups should acquire the same amount of non-associative tolerance.Only the DC group, however, ■may acquire greater overall tolerance due to associative tolerance.According to previous studies, associative tolerance may be explained in terms of classical conditioning.The purpose of this meta-analysis was to determine if associative tolerance exists and to identify which variables may significantly moderate the acquisition of associative tolerance.Effect sizes (d) were calculated for 27 studies and study variables were coded.The DC group acquired greater tolerance (associative tolerance) than the HC group.The inter-dose interval or hours between each conditioning trial, the ratio of dose and inter-dose interval, the number of morphine injections, type of distinctive cue (interoceptive or exteroceptive), and the duration of time the rat was exposed to the distinctive cue after an injection of morphine were significant moderators of the acquisition of associative tolerance.The explanation of the moderator results are explored.* Cepeda-Benito, A. & Tiffany, S. T. (1993).Morphine as a cue in associative tolerance to morphine's analgesic effects.Pharmacology Biochemistry and Behavior 46 149-152.* Cepeda-Benito, A. & Tiffany, S. T. (1995).Role of drug-administration cues in the associative control of morphine tolerance in the rat.Psychopharmacology, 122 312-316.* Cepeda-Benito, A. & Tiffany, S. T. (1996).Unsignaled morphine delivery does not disrupt the development of associative morphine tolerance in the rat.
Author: Amy S. Johnson
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W104825023