Lesion of the bulbospinal noradrenergic pathways blocks desipramine-induced inhibition of the C-fiber evoked nociceptive reflex in rats.
Desipramine-induced inhibition of spinal cord nociceptive transmission was studied in rats with or without lesion of the bulbospinal noradrenergic system by recording the C-fiber evoked nociceptive reflex from a hind limb. Bulbospinal noradrenergic projections were lesioned by injecting intrathecally 20 microg of 6-hydroxydopamine 2 weeks before the electrophysiological experiments. Results show that desipramine (5, 10 and 20 mg/kg intraperitoneally) produced dose-dependent inhibition of the C reflex response duration in rats having intact noradrenergic bulbospinal systems. The inhibitory effect of desipramine was reduced or even abolished in rats pre-treated with 6-hydroxydopamine. In addition, [3H]-noradrenaline uptake was significantly lower in spinal cord slices arising from 6-hydroxydopamine lesioned animals, as compared to that from intact rats. These observations support the notion that the antinociceptive activity of antidepressants with noradrenergic selectivity depends on a normal rate of endogenous noradrenaline released by bulbospinal neurons.
Hernández
A
A
Departamento de Ciencias Biológicas, Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago, Chile.
Laurido
C
C
Mondaca
M
M
Pelissier
T
T
Burgos
H
H
Soto-Moyano
R
R
D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism; D009434:Neural Pathways / Q000293:injuries; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D016627:Oxidopamine; D003891:Desipramine; D009638:Norepinephrine