Influence of Intracerebroventricular Administration of Histaminergic Drugs on Morphine State-Dependent Memory in the Step-Down Passive Avoidance Test

Abstract

The effects of histaminergic drugs on morphine state-dependent memory of a passive avoidance task were examined in mice. Pre-training administration of morphine (5 mg/kg) led to state-dependent learning with impaired memory recall on the test day which was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular (i.c.v.) administration of the H₁ blocker (pyrilamine) prevented the restoration of memory by morphine. The H₂ blocker (ranitidine) was ineffective in this regard and the H₃ blocker (clobenpropit) potentiated the effect of morphine on memory recall. The pre-test i.c.v. administration of histamine alone (5, 10, and 20 µg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. The effect of histamine on memory recall was not changed by the pre-test administration of µ-opioid receptor antagonist, naloxone. In conclusion, the improvement of memory recall by morphine treatment, on the test day, seems to be, at least in part, through the release of histamine followed by the stimulation of H₁ receptors. Histamine by itself, when administered on the test day, mimicked morphine-induced memory improvement by a mechanism independent of the µ-opioid receptors.