PAVLOVIAN MEDIATION OF DRUG SELF-ADMINISTRATION

Recent theories of the etiology of drug addiction suggest that craving and
relapse are linked to a Pavlovian process whereby the drug user learns to
associate environmental cues with drug effects. If the individual returns
to an environment where the drug is expected, but not administered, he may
experience an adverse conditioned physiological reaction similar to
withdrawal which prompts renewed drug taking. Pavlovian conditioned
responses have also been shown to contribute to the growth of drug
tolerance. No study, however, has yet shown a direct link between
conditioned drug responses and self-administration. Using an animal (rat)
model for intravenous self-administration of morphine, we propose several
studies to examine the interplay between Pavlovian conditioning and operant
self-administration. Using both dependent and nondependent rats, several
studies will assess the role of critical conditioning parameters
(interstimulus interval, drug dose, number of trials) on the classical
conditioning of heart rate and body temperature by morphine and naloxone.
We will also see whether the environment associated with drug
self-administration becomes capable of eliciting conditioned physiological
responses and whether such responses are correlated with the frequency of
self-administration. Finally, we will manipulate the Pavlovian value of
contextual cues by pairing them with morphine or naloxone; the behavioral
impact of this conditioning on self-administration will then be assessed.
The results of these studies will permit us to evaluate suggestions that
Pavlovian conditioned responses play a critical role in the development,
maintenance, elimination and relapse of drug addiction. The long term
objective of this research is to increase our understanding of the
biobehavioral processes that contribute to the etiology of drug abuse and
dependence. This understanding should help us to recognize increased risk
of drug abuse, to devise more efficient and effective treatments for drug
addiction and to outline more effective prevention strategies.