title: Associative and nonassociative tolerance: the effects of dose and interdose interval.
abstract: Two experiments examined the effects of dose and interdose interval (IDI) on associative and nonassociative tolerance to morphine analgesia in rats. Associative contingencies were manipulated by administering low (5 mg/kg) or high (20 mg/kg) doses of morphine explicitly paired or unpaired with a distinctive context. Nonassociative processes were manipulated by administering morphine at a short (6-h) or long (96-h) IDI. Tolerance was assessed as shifts in morphine dose-response curves on the tail-flick test. Animals in the long IDI conditions showed considerable context-specific tolerance. Tolerance in the short IDI conditions was not influenced by contextual contingencies at the immediate test (Experiment 1) and showed no retention over a 30-day interval (Experiment 2), suggesting this tolerance was nonassociative. The impact of massed exposure to morphine and context on the disruption of learning at the short IDI is discussed.
authors.affiliation: Psychology Department, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Cox
authors.forename: S T
authors.initials: ST
authors.lastname: Tiffany
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine