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Influence of intracerebroventricular administration of histaminergic drugs on morphine state-dependent memory in the
Mohammad R Zarrindast1, Azita Khalilzadeh, S Mehdi Rezayat
1Department of Pharmacology, School of Medicine, Teheran University of Medical Sciences, Teheran, Iran. zarrinmr@ams.ac.ir
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 H(1) blocker (pyrilamine) prevented the restoration of memory by morphine. The H(2) blocker (ranitidine) was ineffective in this regard and the H(3) blocker (clobenpropit) potentiated the effect of morphine on memory recall. The pre-test i.c.v. administration of histamine alone (5, 10, and 20 microg/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 mu-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 H(1) receptors. Histamine by itself, when administered on the test day, mimicked morphine-induced memory improvement by a mechanism independent of the mu-opioid receptors.
Insights
Morphine-induced memory recall in mice depends on histamine release and H(1) receptor activation. Histamine administration alone also improved memory, independent of opioid receptors.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Opioid drugs like morphine can induce state-dependent learning, where memory recall is contingent on the drug's presence.
- Histaminergic systems play a role in various cognitive functions, including memory.
Purpose of the Study:
- To investigate the role of histaminergic drugs in modulating morphine-induced state-dependent memory in mice.
- To elucidate the specific histamine receptor subtypes involved in this memory phenomenon.
Main Methods:
- Mice were trained under morphine (5 mg/kg) to establish state-dependent learning.
- Memory recall was tested with or without morphine administration.
- Histaminergic drugs (H(1), H(2), H(3) blockers) and histamine were administered intracerebroventricularly (i.c.v.) before testing.
- Naloxone (mu-opioid receptor antagonist) was used to assess opioid receptor involvement.
Main Results:
- Morphine pre-training impaired recall, which was restored by pre-test morphine.
- H(1) blocker (pyrilamine) blocked morphine-induced memory restoration.
- H(2) blocker (ranitidine) was ineffective; H(3) blocker (clobenpropit) potentiated morphine's effect.
- Histamine i.c.v. mimicked and enhanced morphine's memory-improving effect.
- Histamine's effect was independent of mu-opioid receptors.
Conclusions:
- Morphine enhances memory recall, at least partly, via histamine release and subsequent H(1) receptor stimulation.
- Histamine administration alone can improve memory recall through a mechanism independent of mu-opioid receptors.
