Antinociception following microinjection of dibutyryl cyclic nucleotides into the caudal reticular formation and periaqueductal gray of the rat brain.

The tail flick, paw pinch, and hot plate tests were used to assess changes in nociceptive threshold following microinjection of dibutyryl derivatives of cyclic nucleotides into areas of the central nervous system previously shown to be involved in modulation of nociceptive threshold and mediation of morphine analgesia. An elevation in the nociceptive threshold was observed on all three tests following administration of 10 micrograms dibutyryl cyclic 3':5' adenosine monophosphate (db cAMP) into the caudal brainstem reticular formation (CRF) and periaqueductal gray (PAG). Two micrograms db cAMP produced the same magnitude of analgesia but had a shorter duration of action. Twenty micrograms dibutyryl cyclic 3':5' guanosine monophosphate (db cGMP) produced analgesia on all three tests following microinjection at CRF sites but not at PAG sites. These data indicate that morphine analgesia and the antinociception produced by cyclic nucleotides may involve, at least in part, common neuronal substrates. However, the observed capacity of db cAMP to elevate nociceptive threshold does not support the hypothesis that the mechanism of morphine's analgesic action involves inhibition of adenylate cyclase.