Rolipram attenuates MK-801-induced deficits in latent inhibition.
Latent inhibition is used to examine attention and study cognitive deficits associated with schizophrenia. Research using MK-801, an N-methyl-D-aspartate (NMDA) open channel blocker, implicates glutamate receptors in acquisition of latent inhibition of cued fear conditioning. Evidence suggests an important relationship between NMDA-induced increases in cyclic adenosine monophosphate (cAMP) and learning and memory. The authors examine whether amplification of the cAMP signaling pathway by rolipram, a selective Type 4 cAMP phosphodiesterase inhibitor, reverses MK-801-induced impairments in latent inhibition. One day before training, mice were injected with MK-801, rolipram, MK-801 and rolipram, or vehicle and received 20 preexposures or no preexposures to an auditory conditioned stimulus (CS). Training consisted of 2 CS-footshock unconditioned stimulus pairings. Rolipram attenuated the disruptive effect of MK-801 on latent inhibition, which suggests a role for the cAMP signaling pathway in the task and implicates phosphodiesterase inhibition as a target for treating cognitive impairments associated with schizophrenia.
Davis
Jennifer A
JA
Temple University, Department of Psychology, Philadelphia, PA 19122, USA.
Gould
Thomas J
TJ
D000818:Animals; D000242:Cyclic AMP; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate; D020889:Rolipram / Q000494:pharmacology*; D012559:Schizophrenia; D015398:Signal Transduction
D018691:Excitatory Amino Acid Antagonists; D010726:Phosphodiesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000242:Cyclic AMP; D020889:Rolipram