CENTRAL CATECHOLAMINERGIC MODULATION OF CARRAGEENAN-INDUCED PEDAL EDEMA IN RATS

Intracerebroventricularly (i.c.v.) administered noradrenaline (NA) and L-dopa, but not dopamine (DA), attenuated carrageenin-induced pedal oedema in rats. Centrally administered reserpine and the catecholaminergic neurotoxin, 6-hydroxydopamine (6-HD), augmented the inflammatory oedema. Pharmacological treatments, which selectively increase central DA, induce DA neurone degeneration and affect DA receptor activity, were singularly ineffective in modifying the inflammatory response of carrageenin. Centrally administered phentolamine, and .alpha.-adrenergic receptor antagonist, produced a dose-related dual effect on the peripheral oedema. Lower doses of phentolamine produced a paradoxical NA-like oedemaattenuating effect, which was not evident in 6-HD-treated rats; however, a larger dose of the drug had no per se effect but antagonised the oedema-inhibiting effect of centrally administered NA. Propranolol, a .beta.-adrenergic receptor antagonist produced inconsistent effects, with a lower and higher dose of the drug showing no effect, while a median dose induced an inhibitory effect on the peripheral oedema. Bilateral adrenalectomy failed to antagonise the anti-inflammatory effect of central NA, but peripheral degeneration of sympathetic neurones, induced by i.p. administered 6-HD, inhibited the effect of NA. The results of the study indicate that central NA, but not DA, exerts a modulatory inhibitory effect on peripheral oedema induced by carrageenin. This effect of central NA appears to be dependent upon the peripheral sympathetic system and not on the activation of the adrenal corticoid activity.