Interactions of MK-801 and GYKI 52466 with morphine and amphetamine in place preference conditioning and behavioural sensitization.
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.
Tzschentke
T M
TM
Zoological Institute, University of Tübingen, Department of Neuropharmacology, Germany. neuropha@uni-tuebingen.de
Schmidt
W J
WJ
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D014151:Anti-Anxiety Agents; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; D001569:Benzodiazepines; D016291:Dizocilpine Maleate; D009020:Morphine; D000661:Amphetamine