The effects ofl-histidine, and of specific histamine receptor agonists, on the expression of morphine tolerance and physical dependence in mice

Abstract

The effects of L-histidine, and of the specific histamine receptor agonists 2-methylhistamine and 4-methylhistamine, on the expression of morphine tolerance and physical dependence have been studied in mice. These agents were administered during the "withdrawal" phase of development. All of them significantly increased tolerance but reduced the degree of physical dependence. The effects of 2-methylhistamine, which has predominantly H1-receptor activity, were completely abolished by the prior administration of the H1-antagonist mepyramine. The H2-antagonist metiamide, on the other hand, did not alter the action of 2-methylhistamine on physical dependence, though tolerance was restored to its original level. The effects of 4-methylhistamine, which is a specific H2-receptor agonist, were inhibited by metiamide, but mepyramine was unable to reverse the actions of this agonist. The effects of L-histidine, the major precursor of brain histamine, were unaltered by mepyramine, but partially inhibited by metiamide. These experimental findings are discussed in detail, and are considered to give further support to the view that histamine is implicated in some way in the mechanisms of the "withdrawal" phase of morphine tolerance and physical dependence in mice, with H2-receptors probably playing the more important role.

The effects of 4-imidazolyl-3-amino-2-butanone (McN-A-1293), a specific histidine decarboxylase inhibitor, on the expression of morphine tolerance and physical dependence in mice

“…However, while tolerance is inhibited, physical dependence (at least, on the basis of body weight loss) is enhanced by the presumed decrease in brain histamine levels caused by McN-A-1293. This is in line with previous findings [3,4]. These opposite actions on the two phenomena, tolerance and physical dependence, indicate some fundamental difference in their underlying mechanisms, but nevertheless histamine would appear to be involved in some way with both o f them.…”

“…The effect of the histidine decarboxylase inhibitor MeN-A-1293 on morphine tolerance is consistent with the results observed after histamine receptor blockade [3], and opposite to the results obtained with procedures which raise brain histamine levels [3,4].…”

“…The possible involvement of brain histamine in the mechanisms of morphine tolerance and physical dependence has been the subject of recent published work [1][2][3][4]. In our publications [3,4], the effects of L-histidine, histamine, histamine receptor agonists and antagonists on morphine tolerance and physical dependence have been studied.…”

“…In our publications [3,4], the effects of L-histidine, histamine, histamine receptor agonists and antagonists on morphine tolerance and physical dependence have been studied. The present communication reports the effects of a specific histidine decarboxylase inhibitor, McN-A-1293 (4-imidazolyl-3-amino-2-butanone [5]), on tolerance to, and physical dependence on, morphine in mice.…”

The effects ofd-histidine on the expression of morphine tolerance and physical dependence in mice

“…This precursor is able to cross the blood-brain barrier, and whole brain histamine can be increased 2-3 times after a single dose of L-histidine [4,5]. Elevating brain histamine levels in this way has been shown to inhibit the induction of morphine physical dependence [6], as well as to modify the expression of both tolerance and physical dependence in mice [2,7]. It was considered of interest to investigate under comparable conditions the effects of the stereoisomeric o-histidine, as this compound would not be expected to increase histamine'levels.…”