Behavioural Brain Research 117 (2000) 215 – 220 Short communication 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 Luciana A. Izquierdo a , Daniela M. Barros a , Jorge H. Medina b , Iva ´n Izquierdo a, * a Centro de Memoria, Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Uniersidade Federal do Rio Grande do Sul, Ramiro Barcellos 2600, (90035 -003) Porto Alegre, RS, Brazil b Instituto de Biologia Celular y Neurociencia ‘Eduardo de Robertis’, Facultad de Medicina, Uniersidad de Buenos Aires, Paraguay 2255, 3er. Piso, (1121) Buenos Aires, Argentina Received 26 April 2000; received in revised form 10 July 2000; accepted 10 July 2000 Abstract 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-l 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 g), the AMPA receptor blocker, 6,7-cyanonitroquinoxaline-2,3-dione (CNQX, 1.25 g), the generic glutamate metabotropic receptor antagonist, -methyl-(4-carboxyphenyl)glycine (MCPG), the inhibitor of cAMP-dependent protein kinase (PKA), Rp-cAMPs (0.1 or 0.5 g), or the inhibitor of the mitogen-activated protein kinase (MAPK), PD098059 (10 or 50 M). 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. © 2000 Elsevier Science B.V. All rights reserved. Keywords: Novelty; Retrieval, effect of novelty on; AMPA glutamate receptors; NMDA glutamate receptors; cAMP-dependent protein kinase; Mitogen-activated protein kinase; CA1 www.elsevier.com/locate/bbr 1. Introduction Retrieval of one-trial step-down avoidance is inhib- ited by the bilateral infusion into the dorsal CA1 area of the rat hippocampus [1,10,13,20] or in other areas of the cortex [1] of antagonists of AMPA/kainate or metabotropic glutamate receptors, or inhibitors of the cAMP-dependent protein kinase (PKA), of the mito- gen-activated protein kinase (MAPK) chain, or of the protein kinase C (PKC) signalling pathways, but not by an inhibitor of calcium/calmodulin kinase II (CaMKII) [1,13]. The effect of the drugs is not due to influences on locomotion, exploration or anxiety, since the treat- ments had no effect on behaviour in an open-field or a plus-maze [13,20]. The enzymatic cascades mentioned are activated by glutamate receptors [6,15,20], there is ample cross-talk between them [15,20] and all had been previously been shown to be involved also in consolida- * Corresponding author. Tel.: +55-51-316-5530; fax: +55-51-316- 5540. E-mail address: izquier@zaz.com.br (I. Izquierdo). 0166-4328/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0166-4328(00)00286-2