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Chapter 6. Tolerance, Sensitization, Dependence, and Addiction
Essay questions.
Q. A researcher is investigating some of the behavioral properties of a new drug called “GR1944” (a
hypothetical drug). She trains two groups of rats on tasks in which bar pressing is occasionally reinforced with
food. For GROUP DRLR rats the longer the interval between bar presses the greater the likelihood that a bar
press will be rewarded, so GROUP DRLR rats generally press the bar fairly infrequently. For GROUP DRHR
rats the shorter the interval between bar presses the greater the likelihood that a bar press will be rewarded, so
GROUP DRHR rats press the bar fairly rapidly. After the two groups are trained over several daily sessions to
the point that their responding is at stable levels, the researcher splits the two groups into two subgroups. For
five successive daily test sessions, she injects GROUP DRLR-1 and GROUP DRHR-1 rats with 100 mg of
GR1944 30 minutes prior to each session, and for five successive daily test sessions, she injects GROUP DRLR-
2 and GROUP DRHR-2 rats with saline 30 minutes prior to each session. The researcher measures the rate of
bar pressing for each group over the five test sessions.
The researcher notes that after the first injection of GR1944, the GROUP DRLR-1 and GROUP DRHR-1 rats
respond much more frequently than their counterpart controls (i.e., GROUPs DRLR-2 and DRHR-2). However,
by the fifth test session, the GROUP DRLR-1 rats are responding at about the same level as the GROUP DRLR-
2 rats, i.e., it appears that tolerance to GR1944 has occurred. On the other hand, by the fifth test session, the
GROUP DRHR-1 rats are still responding much faster than the GROUP DRHR-2 rats, i.e., tolerance to
GR1944 does not appear to have occurred.
1. Are these observations more compatible with a pharmacodynamic or a context-specific mechanism
for tolerance development? Explain your reasoning.
A (p. 101, 103-105). Since both groups DRLR-1 and DRHR-1 were given the same amount of GR1944
over the same time intervals and only one group exhibited tolerance, a pharmacodynamic mechanism
can be ruled out, leaving a context-specific mechanism resulting from the fact that the task
requirements for the two groups of rats were very different. Specifically, group DRLR-1 rats would
have lost reinforcers upon exposure to GR1944 because it resulted in them responding more frequently,
whereas group DRHR-1 rats would likely increase their reinforcement rate with the drug because the
responded even more rapidly than without the drug. Thus, one would predict that group DRLR-1 rats
would learn some compensatory instrumental behaviors that resulted in them decreasing their rate of
responding to reestablish their original rate of reinforcement, i.e., show tolerance. Since there would be
nothing for group DRHR-1 rats to compensate for, they would show no tolerance.
2. Do these observations tell us anything regarding the question of whether GR1944 is capable of
inducing physical dependence? Explain your reasoning.
A (p. 112-117). This doesn’t tell us much about whether GR1944 could produce physical dependence
because, although tolerance always precedes physical dependence, there are a variety of tolerance
processes that are not linked to physical dependence. However, since the drug was only given once a
day, and only for five days, and tolerance only occurred in one group, it is not likely that, at least with
this dose and dosing interval and number of doses, physical dependence would result. But we don’t
know about whether higher doses, more frequent dosing, or more doses could induce physical
dependence. Furthermore, we would have to see if any signs of abstinence, that were essentially
opposite to the direct effects of the drug, would occur upon drug cessation.
Q. John Key has been injecting the drug Sopor to get “high” four to six times daily for a month. In addition to
the euphoria experienced, the drug induces low blood pressure, low heart rate, pupillary constriction, and
constipation. If John were to immediately stop taking Sopor, what might the abstinence syndrome look like and
what would be its likely time course (described in terms of duration and intensity)?