Situational specificity of tolerance to decreased operant responding by morphine and l-nantradol.

In one experiment, key pressing of rats was maintained under a fixed-ratio schedule of food presentation in a first daily session in one environmental situation, and interruption of a photobeam was maintained under a continuous shock avoidance schedule in a second daily session in another environmental situation. After receiving acute injections of the cannabinoid l-nantradol (0.01-0.3 mg/kg), rats received daily administration of a rate-decreasing dose of the drug after the second session, then before the second session, and then before the first session. Tolerance that developed to decreased avoidance responding in the second daily session did not extend to decreased fixed-ratio responding in the first daily session, but was specific to circumstances coinciding with the pharmacological actions of l-nantradol. In a second experiment lever pressing of squirrel monkeys was maintained under an identical fixed-interval schedule of food delivery in two separate daily sessions in different experimental situations. After receiving once-weekly acute injections of morphine (0.3-3.0 mg/kg), monkeys received daily administration of a rate-decreasing dose of morphine in a counter-balanced order before each session. Just as for experiment 1, tolerance that developed in the environment coinciding with the pharmacological actions of morphine did not immediately generalize to operants in the other environmental situation. Instead, tolerance depended on both pharmacologic action as well as concurrently operating behavioral processes.