Nantradol Tolerance in an Avoidance Task Did Not Transfer Immediately to Food-Maintained Responding

Tolerance to the cannabinoid l-nantradol depended on the circumstances in which rats experienced its effects. Tolerance developed in one task and setting without automatically extending to a different daily session.

Drug timing was linked to the behavioral session

Rats performed food-maintained responding in one daily situation and shock-avoidance responding in another. Investigators moved repeated administration from after the sessions to before particular sessions. This made it possible to examine whether adaptation accompanied drug exposure generally or the circumstances in which the drug acted.

The acquired tolerance did not generalize automatically

Tolerance to decreased avoidance responding in the second session did not extend to decreased fixed-ratio food responding in the first. The finding supports a contribution from behavioral processes operating during drug action. Because both task and setting differed, it does not isolate a single environmental cue as the sole cause.

The opioid comparison was a separate experiment

A second experiment used morphine in squirrel monkeys performing the same schedule in different situations. Its contextual pattern supported the broader behavioral interpretation, but it was not a cannabinoid experiment in the same rats. Species, drug and task should remain attached to each result rather than being blended into one exposure group.

Interpreting the evidence

The study supports conditional transfer of tolerance, not a rule that tolerance always depends on learning. It does not establish an individual's ability to transfer cannabis tolerance between ordinary activities or driving environments.

Related reading: endogenous ligands administered as experimental drugs.

Research reference

Smith JB (1991). Situational specificity of tolerance to decreased operant responding by morphine and l-nantradol. Psychopharmacology. doi:10.1007/BF02244085. Evidence basis: study abstract.

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