DRUG RECEPTORS, NEUROTRANSMITTERS AND ADDICTION

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This project focuses on various drugs of abuse and the receptors with which they interact. We completed a study examining the binding of PCP and related compounds at the cocaine receptor. The relative potencies of these compounds were such that some of the behavioral effects of PCP might be related to its action at the cocaine receptor; in other words, the affinity of PCP at the cocaine binding site was interesting but considerably less than its affinity at its own receptor. (Ki of 1.59 mM vs a Ki of about 0.12 mM). Thus, at high blood levels, PCP could interact with the cocaine receptor but it would most likely occupy the PCP site at the NMDA receptor at much lower concentrations. Another study examined the movement of opiate receptors within neurons. Receptors are synthesized by the usual protein synthetic machinery of cells. They are then transported to sites and inserted into the membrane. We examined the transport of opiate receptors in rat vagus and in dorsal roots of spinal nerves. We found that the opiate receptors were transported in these neurofibers by fast transport and this agrees with many studies of other receptors. The binding sites in the axons had properties similar to those for receptors observed in brain tissue; the binding sites had appropriate pharmacology, were GTP sensitive as well as showed effects of sodium.