The effects of opiates on the levels of cyclic 3':5'-guanosine monophosphate in discrete areas of the rat central nervous system

O'Callaghan, J.P.; Chess, Q.; McKimmey, C.; Clouet, D.H.

Journal of Pharmacology and Experimental Therapeutics 210(3): 361-367

1979


ISSN/ISBN: 0022-3565
PMID: 225468
Document Number: 146077
Following tissue fixation by focused microwave irradiation, the levels cGMP were measured in mg samples from 6 discrete areas of the rat brain using a femtomole-sensitive radioimmunoassay combined with a microdissection technique. The acute administration of morphine produced a dose- and time-dependent reduction in levels of cGMP in the periaqueductal gray (PAG) and centromedian thalamus regions; an effect that could be antagonized by the prior administration of naloxone. The effect of morphine was site-specific since cGMP levels remained unchanged in the caudate putamen, ventromedial hypothalamus, lateral hypothalamus and pituitary. Subjects rendered tolerant to the effects of morphine by the implantation of morphine pellets were tolerant to the morphine-induced depletion of cGMP in the PAG. The effect of morphine on cGMP in the PAG was shared by the morphine congener, levorphanol, but not by its inactive stereoisomer, dextrorphan. The mixed agonist/antagonist drugs, pentazocine and cyclazocine, also caused a reduction in cGMP in the PAG and did not affect cGMP levels in other brain areas. The administration of CNS active agents at doses causing overt behavioral depression resulted in a depletion cGMP that was not limited to the PAG region. The morphine-induced depletion of cGMP on the PAG did not appear to be to an interaction with stress-related changes in cGMP. Some of the analgesic effects of opiates are apparently mediated by a cGMP system in the PAG with the analgesic response corresponding to a depletion of cGMP in this area.

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