Behavioural Brain Research 154 (2004) 339–343 Research report Protein synthesis, PKA, and MAP kinase are differentially involved in short- and long-term memory in rats João Quevedo a,b,∗ ,Mˆ onica R.M. Vianna b , Márcio Rodrigo Martins a , Tatiana Barichello a , Jorge H. Medina c , Rafael Roesler d , Ivan Izquierdo b a Laboratório de Neurotoxicologia, Universidade do Extremo Sul Catarinense, Av. Universitaria 1105, Criciúma 88806-000, SC, Brazil b Departamento de Bioqu´ ımica, Centro de Memória, Instituto de Ciˆ encias Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil c Laboratório de Neurorreceptores, Instituto de Biologia Celular y Neurociˆ encia Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina d Laboratório de Neurofarmacologia Pré-clinica, Departamento de Farmacologia, Instituto de Ciˆ encias Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90046-900, RS, Brazil Received 29 August 2003; received in revised form 9 February 2004; accepted 3 March 2004 Available online 17 April 2004 Abstract We studied the involvement of hippocampal protein synthesis-, PKA-, and MAP kinase-dependent processes in short- (STM) and long-term memory (LTM) for inhibitory avoidance task. Fifteen minutes before or immediately after training rats received intrahippocam- pal infusions of vehicle, the protein synthesis inhibitor anisomycin, the PKA inhibitor Rp-cAMPs or the MAPKK inhibitor PD098059. The results show that STM recruits PKA and MAPK, whereas, LTM depends on PKA activity and protein synthesis during the early post-training period. © 2004 Elsevier B.V. All rights reserved. Keywords: Short-term memory; Long-term memory; Hippocampus; Protein synthesis; cAMP-dependent protein kinase (PKA); Mitogen-activated protein kinase (MAPK) 1. Introduction Memory is not a unitary process and a single learning experience can initiate processes with different durations and specific biological purposes. According to duration there are two major forms of memory: short-term memo- ries (STMs) lasting from minutes to hours and long-term memories (LTMs) lasting days, weeks, and even a life time. Since William James (1890) [17] made the distinc- tion between these two types of memory a major question in neurobiology was whether STM was merely an initial stage of LTM formation or an independent phenomena. For almost a century, attempts to disengage STM from LTM failed mostly due to methodological limitations that made impossible the separation of simultaneous processes sharing common neuroanatomical and neural substrates. ∗ Corresponding author. Fax: +55-48-431-2750. E-mail address: quevedo1@terra.com.br (J. Quevedo). For these reasons most of the efforts to understand the neuroanatomical, cellular, and molecular basis of memory processing concentrated on LTM. A unique characteristic of LTM is the requirement of a consolidation period during which synaptic, structural, and functional modifications take place to enable its long-lasting maintenance. Recent studies from our laboratory have shown that, for the one-trial inhibitory avoidance task, a STM memory system operates separately from LTM formation in the hippocampus and related brain areas. Thus, several pharma- cological treatments block STM leaving LTM intact, when given into the hippocampus, entorhinal, parietal cortex, and prefrontal cortex [14–16,27,28]. Some mechanisms under- lying STM overlap with those of LTM consolidation, but several others are independent or operate at specific time periods [14–16]. A distinguishing characteristic of long-term memory (LTM) is its sensitivity to inhibitors of protein synthesis [4,7,9,10,23,25,26]. Most findings argue that the critical time for protein synthesis is during or immediately after 0166-4328/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2004.03.001