Tolerance may involve classical conditioning processes. A
conditioned drug opponent response is thought to increase with drug
exposures and summate with the unconditioned response to the drug
resulting in tolerance.
A classic study by Siegel, Hinson, Krank, and McCully (1982)
was one of the first to demonstrate this. The researchers found
that rats can be classically conditioned to develop tolerance to
heroin.
Siegel, et al. (1982) wanted to understand why some addicts
died after taking a dose of the drug that they had taken many times
before.
The official cause of death in these cases usually was said to
be a “drug overdose” because the dose was high enough to kill most
people not addicted to the drug. These addicts, however, had
developed a high level of tolerance to the lethal effects of the
drug, so ascribing their deaths to an overdose couldn’t be
correct.
The researchers hypothesized that the addicts’ tolerance was
due, in part, to classical conditioning.
That is, the situation is which they typically took the drug
had become a conditioned stimulus (CS) that elicited a conditioned
response (CR) involving a change in biological processes that
prepared their bodies to counteract the lethal effects of the
drug.
Siegel, et al. (1982) designed an experimental study to test
the classical-conditioning theory of drug tolerance. They gave rats
injections of heroin every other day for 30 days (a total of 15
injections). They increased the dose gradually over time so that
the rats eventually could tolerate relatively high doses.
At the end of the 30-day period, rats in all three groups were
given a very large dose of heroin.The lcontrol group rats that were
injected only with the sugar solution during the first part of the
experiment.Almost all the rats in the Control Group died after
being injected with the large dose of heroin because they had no
tolerance for its lethal effects.
Siegel, et al. (1982) interpreted these results as supporting
their theory: the environmental stimuli in which drug addicts
usually take the drug serve as a CS that produces a CR that
increases tolerance for the drug’s effects.