Pretraining but not Preexposure to the Task Apparatus Prevents the Memory Impairment Induced by Blockade of Protein Synthesis, PKA or MAP Kinase in Rats

Neurochemical Research, Vol. 30, No. 1, January 2005 ( 2005), pp. 6167

DOI: 10.1007/s11064-004-9686-3Pretraining but not Preexposure to the Task Apparatus

Prevents the Memory Impairment Induced by Blockade

of Protein Synthesis, PKA or MAP Kinase in RatsJoao Quevedo,1,6 Monica R. M. Vianna,2 Rafael Roesler,3 Marcio Rodrigo Martins,1

Fernanda de-Paris,4 Jorge H. Medina,5 and Ivan Izquierdo4(Accepted September 20, 2004)Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task(0.4 mA footshock, 24 h training-test interval). Fifteen minutes before or 0, 1.5 or 3 hours

after training, animals received a 0.8 ll intrahippocampal infusion of the protein synthesis

inhibitor anisomycin (80 lg), the PKA inhibitor Rp-cAMP (0.05 lg), the MAPK kinase

inhibitor PD 098059 (50 lM solution) or vehicle (phosphate buer in saline, pH 7.4).

Anisomycin, Rp-cAMP and PD 098059 impaired retention test performance in animals

injected at dierent times, prior and after training. Pretraining with a low footshock intensity (0.2 mA) 24 h before training prevented the amnestic eect of all drugs studied. However, simple preexposure to the inhibitory avoidance apparatus did not alter the amnestic

eects of all drugs. The results suggest that memory processing requires hippocampal mechanisms dependent on protein synthesis, PKA and MAPK kinase at dierent times after

training. These ndings suggest that weak training must be sucient to produce some lasting cellular expression of the experience so that the enhancement of consolidation of a previously acquired memory is not dependent on protein synthesis, PKA or MAPK.KEY WORDS: MAPK; memory; PKA; Protein synthesis; rat.1 Laboratorio de Neurociencias, Universidade do Extremo SulCatarinense, 88806-000 Criciuma, SC, Brazil.2 Montreal Neurological Institute, McGill University, Montreal,Quebec, Canada H3A 2B4.3 Departamento de Farmacologia, Instituto de Ciencias Basicasda Saude, Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, RS, Brazil.4 Departamento de Bioqumica, Centro de Memoria, Instituto deCiencias Basicas da Saude, Universidade Federal do RioGrande do Sul, 90035-003 Porto Alegre, RS, Brazil.5 Laboratorio de Neurorreceptores, Instituto de Biologia Celulary Neurociencia Eduardo de Robertis, Facultad de Medicina,Universidad de Buenos Aires, Buenos Aires, Argentina.6 Adress reprint request to: Joao Quevedo, M. D., Ph.D, Laboratorio de Neurociencias, Universidade do Extremo Sul Catarinense, 88806-000 Criciuma, SC, Brazil. Fax: [phone];E-mail: [email protected] molecular events required for long-term

memory (LTM) consolidation are dependent on protein synthesis (4) at dierent times:...