Environmental specificity of tolerance to morphine-induced analgesia in a terrestrial snail: generalization of the behavioral model of tolerance.

Terrestrial snails, Cepaea nemoralis, develop tolerance to morphine-induced analgesia, such that after 7-9 days of treatment with morphine (10 mg/kg) their response latencies to an aversive thermal stimuli (38.5 degrees C) are not significantly different from those of untreated control animals. In Experiment A snails were rendered tolerant to morphine using either of two pre-injection cues (light and dark background brightness or color) and then assessed for morphine-induced alterations in thermal nociceptive responses in both environments. In Experiment B snails were made tolerant to morphine in the presence of one of two different thermal cues (a stressful temperature of 35 degrees C that is normally avoided or an ambient temperature of 22 degrees C) and then tested for morphine-induced alterations in nociceptive responses in both environments. In the two experiments tolerance to morphine-induced analgesia was displayed when snails were exposed to the pre-injection environmental cue normally associated with the administration of morphine, but not when exposed to the alternative pre-injection cue. These results demonstrate that various environmental factors (background colors or brightness as well as temperature cues and potentially thermal stress), can function as environmental specific cues for the development of tolerance to morphine-induced analgesia in molluscs, in a manner consistent with a behavioral mechanism of tolerance. Thus, these results suggest that environmental specificity of tolerance involving either classical (Pavlovian) conditioning or habituation may be a general phenomenon having an early evolutionary development and broad phylogenetic continuity.