Molecular signalling pathways in the cerebral cortex are required for retrieval of one-trial avoidance learning in rats

Rats were implanted bilaterally with cannulae in the CAI region of the dors al hippocampus, the entorhinal cortex, anterior cingulate cortex, posterior parietal cortex, or the basolateral complex of the amygdala. The animals w ere trained in one-trial step-down inhibitory avoidance and tested 24 h lat er. Prior (10 min) to the retention test, through the cannulae, they receiv ed 0.5 mu l infusions of a vehicle (2% dimethylsulfoxide in saline), or of the following drugs dissolved in the vehicle: the glutamate NMDA receptor b locker, aminophosphonopentanoic acid (AP5, 2.0 or 5.0 mu g), the AMPA recep tor blocker, 6,7-dinitroquinoxaline-2,3 (1H,4H)dione: (DNQX, 0.4 or 1.0 mu g), the metabotropic receptor antagonist, methylcarboxyphenylglycine (MCPG, 0.5 or 2.5 mu g), the inhibitor of cAMP-dependent protein kinase (PKA), Rp -cAMPs (0.1 or 0.5 mu g), the PKA stimulant, Sp-cAMPs (0.5 mu g), or the in hibitor of the mitogen-activated protein kinase (MAPK), PD098059 (10 or 50 mu M). All these drugs, at the same doses, had been previously found to alt er long-term memory formation of this task. Here, retrieval test performanc e was blocked by DNQX, MCPG, Rp-cAMPs and PD098059 and enhanced by Sp-cAMPs infused into CA1 or the entorhinal cortex. The drugs had similar effects w hen infused into the parietal or anterior cingulate cortex, except that in these two areas AP5 also blocked retrieval, and in the cingulate cortex DNQ X had no effect. Infusions into the basolateral amygdala were ineffective e xcept for DNQX, which hindered retrieval. None of the treatments that affec ted retrieval had any influence on performance in an open field or in a plu s maze; therefore, their effect on retention testing can not be attributed to an influence on locomotion, exploration or anxiety. The results indicate that the four cortical regions studied participate actively in, and are ne cessary for, retrieval of the one-trial avoidance task. They require metabo tropic and/or NMDA glutamate receptors and PKA and MAPK activity. In contra st, the basolateral amygdala appears to participate only through a maintena nce of its regular er;citatory transmission mediated by glutamate AMPA rece ptors. (C) 2000 Elsevier Science B.V. All rights reserved.