5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats.
The antinociceptive effect elicited by the 5-hydroxytryptamine (5-HT) agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was reversed or blocked in animals which had previously sustained severe spinal noradrenaline (NA) depletion via either systemic N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4), neonatal 6-hydroxydopamine (neon. 6-OHDA), or intrathecal 6-OHDA treatment. Biochemical analysis of the lumbar spinal cord samples confirmed severe central NA depletions. Animals were tested with nondamaging heat pain (tail-flick test, hot-plate test) and electric footshock titration to determine the amount of antinociception or nociception. Peripheral NA depletion following intravenous (i.v.) 6-OHDA injection to adult rats had no effect on the antinociception induced by 5-MeODMT, but did cause severe NA depletions in the left heart atrium. These results suggest a modulatory effect of central and not peripheral noradrenergic system upon 5-HT agonist induced analgesia, and also give evidence that this effect is spinally mediated.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002490:Central Nervous System / Q000503:physiopathology*; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D010146:Pain / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives* / Q000502:physiology*
D001596:Benzylamines; D006892:Hydroxydopamines; D008732:Methoxydimethyltryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine; C012102:DSP 4; D009638:Norepinephrine