The principal objective of this study is to establish dose-response data for several known and quantifiable effects of narcotics in animals and to apply modern concepts of drug-receptor theory to determine the affinity of the narcotic for its receptor or receptors. These experiments can be expected to shed light on the question of whether or not the several effects of the narcotic are mediated through the same pharmacological receptor and what changes in receptor affinity occur during physical dependence. The determinations will be made in both normal animals and in animals that have been made physically dependent to opiates. Morphine will be the narcotic agent used for most studies. From among the effects in the spectrum of opiate actions, several endpoints will be measured. These include body temperature, heat production (metabolic rate), pupillary size, analgesia and seizure threshold. Narcotic antagonists known to antagonize all of the narcotic-induced responses mentioned above, particularly naloxone, will be employed as agents on whose background the narcotic effects will be quantitated as functions of dose, thus permitting a determination of antagonist affinity for the receptor or receptors under study. To provide further insight into the interrelationships between drug, receptor and effect, dose-response data of the type discussed above will be established in animals whose response to some of the effects of narcotics has been altered by brain lesions or differential housing. A clear definition of drug-receptor interaction in regard to narcotics in both the dependent and non-dependent subject would add significantly to our knowledge concerning opiate mechanisms.
NIH ExPorter
NIH ExPorter