Novelty enhances retrieval of one-trial avoidance learning in rats 1 or 31 days after training unless the hippocampus is inactivated by different receptor antagonists and enzyme inhibitors.

Rats were implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus. The animals were trained in one-trial step-down inhibitory avoidance and tested either 1 or 31 days later. Some of the animals were exposed, 1 h prior to retention testing, to a novel environment. This was a 50-cm high, 50-cm wide and 39-cm high wooden box covered on the inside with black plastic. Through the cannulae, 10 min prior to the retention test, the rats received 0.5-microl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), or of the following drugs: the glutamate NMDA receptor blocker, aminophosphonopentanoic acid (AP5, 5.0 microg), the AMPA receptor blocker, 6,7-cyanonitroquinoxaline-2,3-dione (CNQX, 1.25 microg), the generic glutamate metabotropic receptor antagonist, alpha-methyl-(4-carboxyphenyl)glycine (MCPG), the inhibitor of cAMP-dependent protein kinase (PKA), Rp-cAMPs (0.1 or 0.5 microg), or the inhibitor of the mitogen-activated protein kinase (MAPK), PD098059 (10 or 50 microM). CNQX and PD098059 were dissolved in the vehicle; AP5 and Rp-cAMPs were dissolved in saline. All these drugs except AP5 had been previously found to alter retrieval of this task. Novelty markedly enhanced retention test performance of the avoidance task. The drugs, in accordance with previous results, and with the exception of AP5 at any of the two training-test intervals and of CNQX at the 31-day interval, hindered retention test performance. The results indicate that the effect of novelty on retrieval can not be observed if the major biochemical mechanisms of retrieval (AMPA receptors, PKA, MAPK) are blocked, i.e. if the hippocampus was temporarily inactivated by drugs that inhibit those mechanisms.