Cannabinoid Effects on Operant Responding Were More Resistant to Tolerance Than Temperature Effects in Rats
In a rat experiment, tolerance to a synthetic cannabinoid developed most strongly for reduced body temperature and least strongly for suppressed food-reinforced responding. The effects that occurred readily after acute exposure were not necessarily those that adapted fastest.
Three tests captured different functions
The researchers compared cannabinoid effects on food-reinforced operant behavior, hot-plate reaction latency and body temperature. Acute comparisons included THC, HU-210, WIN 55,212-2 and CP 55,940. The receptor-blockade and repeated-administration comparisons focused on CP 55,940, so those results should not be attributed indiscriminately to every tested cannabinoid.
Blockade was also endpoint-specific
SR141716A blocked hypothermic and antinociceptive effects more effectively than it blocked suppression of response rate. During repeated CP 55,940 treatment, temperature tolerance developed faster and more extensively than tolerance in the operant task. The two comparisons therefore both showed that endpoints differed in their sensitivity.
Temperature normalization did not establish behavioral recovery
A body-temperature response returning toward baseline cannot stand in for preserved task performance. Conversely, suppressed responding in this animal task does not directly measure a person's attention, driving ability or workplace performance. The task provides a controlled behavioral endpoint with its own limits.
This study's specific contribution is the relationship between acute dose sensitivity, antagonist sensitivity and later tolerance across tests. It supports examining the actual function being claimed to recover. A broad assertion of cannabinoid tolerance would conceal the residual behavioral effects that the operant measure was designed to capture.
Related: interpreting cannabis tolerance claims.
Research cited
De Vry J; Jentzsch KR; Kuhl E; Eckel G. Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. Behavioural pharmacology (2004). doi:10.1097/00008877-200402000-00001. Findings discussed from the study abstract.
