A. Cepedabenito et St. Tiffany, ROLE OF DRUG-ADMINISTRATION CUES IN THE ASSOCIATIVE CONTROL OF MORPHINE-TOLERANCE IN THE RAT, Psychopharmacology, 122(3), 1995, pp. 312-316
This research investigated the role of injection procedures as a poten
tial confound in the study of associative and nonassociative morphine
tolerance development. Rats administered a series of morphine injectio
ns paired with a distinctive context environment can develop tolerance
controled associatively by the context. However, rats given morphine
unpaired with the context may also develop some degree of tolerance. T
his study examined whether this tolerance represents an associative ef
fect with animals using the injection ritual as a cue predictive of mo
rphine delivery. Following 14 days of habituation to handling and inje
ction stimuli, rats were given eight morphine injections (20 mg/kg, IP
) explicitly paired or unpaired with a distinctive context. Animals we
re then tested for morphine analgesia in the context after either a 30
-day rest condition or a 30-day period of daily saline injections. Ana
lgesia was assessed by the tail-flick method, and tolerance was define
d as the shift to the right of the dose-response curve of morphine-exp
erienced relative to saline control animals. Paired animals across bot
h retention conditions displayed tolerance, whereas tolerance retentio
n in unpaired animals was observed only in those animals not given sal
ine injections over the 30-day interval. Results support an associativ
e interpretation of tolerance observed in unpaired conditions and sugg
est that the injection ritual may provide highly salient cues for the
support of associative tolerance effects.