Interactions of MK-801 and GYKI 52466 with morphine and amphetamine in place preference conditioning and behavioural...

In an earlier study we showed that co-administration of the NMDA-receptor antagonist MK-801 during conditioning sessions blocks morphine-induced conditioned place preference (CPP). From this result, the question arose of whether this blockade is due to state-dependency effects induced by MK-801. Therefore, in a first experiment, animals were tested in the drugged state under which they had been conditioned. These animals did not show a CPP, thus it can be concluded that MK-801 does not make state-dependent the morphine conditioning. In the same experiment those animals receiving only morphine during conditioning sessions showed a significant CPP when tested in an undrugged state but failed to show CPP when tested after injection of MK-801 (i.e., in the drugged state). These results indicate that MK-801 not only blocks the development of morphine-induced CPP but is also able to block the expression of a conditioned response that has been acquired before. In the same experiment repeated injection of neither morphine nor MK-801 produced sensitized locomotor activity. However, a strong sensitization was observed following repeated injection of morphine plus MK-801. There was also cross-sensitization between morphine plus MK-801 and MK-801 alone but not with morphine alone, and also between morphine and MK-801, but not vice versa. In a second experiment the effects of the AMPA-receptor antagonist GYKI 52466 were examined. It was found that GYKI 52466 did not produce CPP or behavioural sensitization. Finally, in a third experiment, CPP was induced by morphine and amphetamine (animals tested in the drug-free state), and behavioural sensitization was induced by amphetamine. When animals were tested after an injection of GYKI 52466, neither the morphine- nor the amphetamine-conditioned animals showed a CPP. Likewise, challenge of sensitized animals with amphetamine plus GYKI 52466 failed to produce a sensitized response. It can be concluded, that GYKI 52466, like MK-801, can block the expression of a conditioned response, and can also block the expression of sensitized behaviour.