Assessment of the associative determinants of tolerance to the effects of cannabis extract on exploratory behavior in rats

Experimental evaluation of cannabis tolerance has lacked an associative learning approach, focusing primarily on physiological variables. The present study assessed acute effects, chronic tolerance, and contextual specificity, exploring a potential associative component underlying cannabis tolerance. Sixteen adult Sprague-Dawley rats of both sexes were assigned to two groups, one receiving vaporized administrations of cannabis and the other receiving the vehicle substance, in two different counterbalanced contexts. An initial measurement was performed to assess acute effects, followed by four measurements to evaluate the development of chronic tolerance, and a final measurement to test the context specificity of tolerance, comparing the responses to the usual administration context and a novel context. Ten behaviors were analyzed in an open field. Acute effects were observed in seven indicators, corresponding to greater exploration activity in the group that received the drug compared to the control group. In five of these, the data also showed the development of chronic tolerance to the effects of cannabis on exploration, which was indicated by a progressive decrease in exploratory activity in the drug group. However, no evidence of context specificity was found in any variables in which chronic tolerance was observed. We discuss factors that may be related to the lack of contextual specificity of cannabis tolerance. Together, our findings show that a single administration of cannabis induces acute effects, and repeated exposure leads to chronic tolerance, ultimately reducing exploratory behavior.