Noradrenergic-serotonergic interactions and nociception in the rat.
Spinal noradrenaline (NA) depletion in rats, via either systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) or intrathecal 6-hydroxydopamine (6-OHDA), reversed and/or abolished the analgesic effects of the 5-hydroxytryptamine (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA), in shock titration, hot-plate and tail-flick measures of pain sensitivity. Spinal NA depletion also abolished the analgesic effects of 5-HT itself, administered intrathecally, in all three nociception tests and potentiated the analgesic effects of intrathecal NA, a demonstration of receptor supersensitivity. Spinal 5-HT depletion, via intrathecal 5,7-dihydroxytryptamine (5,7-DHT), only attenuated 5-MeODMT-induced analgesia in the tail-flick test but potentiated the 5-MeODMT effect in the hot-plate test. Intrathecal 5,7-DHT treatment caused a drastic potentiation of NA-induced analgesia in the shock titration and tail-flick tests but not in the hot-plate test. Biochemical analyses confirmed the NA and 5-HT depletion. The spinal noradrenergic system appears to be an important tonic factor modulating the function of the descending 5-hydroxytryptaminergic pathway.
Archer
T
T
Jonsson
G
G
Minor
B G
BG
Post
C
C
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*
D001596:Benzylamines; D006892:Hydroxydopamines; D008732:Methoxydimethyltryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine; C012102:DSP 4; D009638:Norepinephrine