Naloxone reversal of 5-hydroxytryptamine tachyphylaxis in humans

The dorsal hand vein, a suitable substrate for testing the effects of spasmogenic amines in vivo, exhibits a rapid tachyphylaxis to 5-hydroxytryptamine (5-HT)-induced vasoconstriction in healthy subjects. In the tachyphylactic vein, naloxone promptly restores and sometimes potentiates the sensitivity to 5-HT. The local opioid system could be excited by the 5-HT-induced release of noradrenaline (NA) into the neuromuscular junction, thereby participating in the 5-HT tachyphylaxis. Naloxone, antagonizing this mechanism, restores the 5-HT spasm. Therefore, the 5-HT tachyphylaxis could be due to an increased opioid modulation and not (or perhaps partially) to a depletion of the NA in the sympathergic neuron.