Tolerance to the morphine-influenced thermal response in the terrestrial snail, Cepea nemoralis.

The terrestrial snail, Cepea nemoralis, displayed stereotyped thermal-avoidance behavior, with morphine increasing and naloxone decreasing the latency of this response. After 5-7 days of daily administration of morphine sulfate (1 microliter of 0.10-10.0 mg/ml) the thermal responses of snails displayed tolerance to morphine. The response latency was reduced to that of saline-treated individuals. Pretreatment with the protein synthesis inhibitor, cycloheximide, blocked the development of tolerance. After termination of chronic treatment with morphine, tolerant snails exhibited withdrawal signs that included increased responsiveness to naloxone, decreased responsiveness to morphine and saline and behavioral alterations suggesting irritation and hyperactivity. These results suggest that the thermally-induced behavior of Cepea can serve as a useful model for the investigation of the development of opioid tolerance and physical dependence in mammals.