MK-801 disrupts acquisition of contextual fear conditioning but enhances memory consolidation of cued fear conditioning.
The effects of pre-training or post-training subcutaneous injections of multiple doses of the non-competitive NMDA-receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on cued and contextual fear conditioning were examined in F344 rats. Pre-training injections of MK-801 (0.3 and 1.0 mg/kg) disrupted contextual fear conditioning but not cued fear conditioning. Post-training injections of MK-801 did not disrupt cued or contextual fear conditioning. In fact, the 0.3 mg/kg dose of MK-801 enhanced cued fear conditioning. Finally, rats were tested for MK-801-induced alterations in sensitivity to pain using the formalin test for nociception. MK-801 did not reduce sensitivity to pain. These results suggest that NMDA receptors are involved in acquisition of contextual fear conditioning but not in memory consolidation of the learned response.
Gould
T J
TJ
CNS Discovery Department, AstraZeneca Pharmaceuticals, Wilmington, DE 19850-5437, USA. tgould@astro.temple.edu
McCarthy
M M
MM
Keith
R A
RA
D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate