Intracerebroventricular Effects of Histaminergic Agents on Morphine‐Induced Anxiolysis in the Elevated Plus‐Maze in Rats

Abstract

Some reports indicate that morphine can induce anxiolytic effects both in animal and in man. It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine-induced anxiolysis in rats, using elevated plus-maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 mg/rat) also increased anxiety-related behaviours. Intracerebroventricular injection of pyrilamine, a H 1 receptor antagonist (25, 50 and 100 mg/rat), increased anxiety whereas injection of ranitidine, a H 2 receptor antagonist (5, 10 and 20 mg/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H 2 receptors, while the response of H 1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 mg/rat), pyrilamine (50 mg/rat) and ranitidine (5 mg/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 mg/rat), pyrilamine (25, 50 and 100 mg/rat) or ranitidine (5, 10 and 20 mg/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety-related indices in the elevated plus-maze. This may imply that morphine-induced anxiolysis probably is independent of the histaminergic system.

Increased anxiety-like behaviors in rats experiencing chronic inflammatory pain

“…In fact, morphine has already been shown to decrease fear-and anxiety-related behaviors in rhesus monkeys [59] and in humans [60]. Furthermore, injection of morphine in healthy rats either has no effect [26] or induces anxiolytic effects [61,62] when tested in the EPM. Part of the explanation for this divergence in morphine effectiveness in relieving anxiety could involve the anxiety-like behavioral test employed, the dose used, the route of administration (systemic vs central vs local injection) and the injection protocol (acute vs sustained).…”

GABA and Histamine Interaction in the Basolateral Amygdala of Rats in the Plus-Maze Test of Anxiety-Like Behaviors

“…Moreover, it has been demonstrated that experimental anxiety can be achieved by coadministration of a neuronal histamine releaser (thioperamide) with a histamine agonist (betahistine) [32] . The anxiogenic effect of histamine and related compounds has also been reported following injection into some brain regions, such as the nucleus basalis magnocellularis [14] , nucleus accumbens [33] , inferior colliculus, periaqueductal gray [34] , cerebroventricle [35] and ventral hippocampus [36] . We also reported an anxiogenic effect following injection of histamine into the central nucleus of the amygdala in our previous study [37] .…”

The Flavonoid Glycosides, Myricitrin, Gossypin and Naringin Exert Anxiolytic Action in Mice

“…First, opiods are clinically known for their potent analgesic action, but they can also cause deep depression of the CNS and potentiate the sedative-hypnotic effects of benzodiazepines [11]. Moreover, preclinical evaluation of morphine has shown that this opioid agonist can induce anxiolysis after both peripheral and central administration [12,13]. Second, it is well accepted that the opioid endogenous system plays a role in the anxiolytic action of benzodiazepines.…”