Physical and psychic dependence on
opioids and
CNS depressants in rodents were examined using the
drug-admixed food (DAF) method. A comparison of several methods for developing physical dependence on
opioids was made. The DAF method has the advantage of rapidly inducing a high degree of physical dependence without causing morbidity or mortality. When
morphine-dependent rats were pretreated with several
opioids,
naloxone-precipitated
weight loss was suppressed in a dose-dependent manner. A procedure for the development of severe physical dependence on
CNS depressants was also established.
Drug concentrations were rapidly increased until animals showed moderate to severe CNS depression, and then this condition was maintained for at least 10 days. With this procedure, animals became severely dependent on
CNS depressants. Another technique, intermittent infusion, was developed that has been used to quantify short-acting CNS depressant dependence potential. The
sedative effects of
pentobarbital were used as an index in the determination of the injection intervals. These results suggest that the DAF method and the new approaches are useful tools for assessing the physical dependence potential of new drugs. Moreover, oral
self-administration and weight pulling procedures were utilized along with the DAF method. Procedures for the oral
self-administration of
opioids and
CNS depressants were established.
Opioid-dependent rats pulled the weight to obtain the DAF even though they had free access to normal food. This weight-pulling procedure may be useful for assessing the degree of reinforcing effects for drugs in rats.