Differentiation of Analgesic Opiate Receptors in Mice by Direct Intraspinal and Intracranial Injections of Various Narcotic-Like Agents
Varner, Kurt J.
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In this project a variety of analgesic drugs were injected intraperitoneally (i.p.), intracranially (i.c.) and intraspinally (i.s.) in mice, followed by testing with both the tail-flick and hot-plate assays. From the patterns of analgesia produced by the different drugs, a determination was made as to the number of opiate receptor types in the CNS. In the first part of the project, the analgetic activities of the morphine-like (µ) and ethylketocyclazocine (k) agonists were compared. The k agonists were seen to produce predominantly spinal analgesia on both assays while the µ agonists were seen to produce site specific analgesic activity within the CNS. This finding indicates the existence of more than one type of analgesic opiate receptor. Intraspinal and intracranial injection of the enkephalin dynorphine and enkephalin analogs were seen to produce extremely potent spinal activity, raising the possibility that the enkephalins may be endogenous k agonists. Central nervous system injection of narcotic antagonists, produced µ-like agonist activity instead of the k-like activity, which would have been predicted by Martin's multiple receptor model (1967, 1976). The lack of analgesic activity produced by the central administration of the antidiarrhoeal drug loperimide, which is believed to be an opiate ligand, suggests the existence of a nonanalgetic opiate receptor.