Cross state-dependent memory retrieval between morphine and norharmane in the mouse dorsal hippocampus

Abstract

State-dependent memory (SDM) describes a phenomenon that memory is efficiently restored only when the brain state during restoration matches the state during encoding. Some psychoactive drugs such as morphine, ethanol, and cocaine evoke SDM. The scope of this study was to investigate the cross SDM between morphine and norharmane injected into the dorsal hippocampus of male NMRI mice, and the involvement of μ-opioid receptors (MORs) in the SDM of the drugs. Bilateral cannulae were implanted into the CA1 regions (intra-CA1), and memory retrieval was measured by the step-down apparatus. Results showed that pre-test microinjection of morphine (1 μg/mouse, intra-CA1) reversed amnesia induced by pre-training administration of the same dose of morphine, indicating morphine SDM. Moreover, norharmane (10 μg/mouse) also exerted a SDM. Pre-test microinjection of naloxone (0.5 μg/mouse) abolished amnesia induced by morphine or norharmane, and impaired SDM produced by each drug. The results demonstrated the contribution of MORs in the SDM induced by morphine as well as norharmane. Pre-test administration of morphine (1 μg/mouse, intra-CA1) also inhibited amnesia induced by pre-training intra-CA1 microinjection of norharmane (10 μg/mouse) and vice versa, suggesting a cross SDM between the drugs. In conclusion, it seems that there may be a cross SDM between morphine and norharmane, and MORs have a critical role in this phenomenon.