DARPP-32 expression in rat brain after an inhibitory avoidance task.

Step-down inhibitory avoidance (IA) is usually acquired in one single trial, which makes it ideal for studying processes initiated by training, uncontaminated by prior or further trials, rehearsals, or retrievals. Biochemical events in the hippocampus related to long-term memory (LTM) formation have been extensively studied in rats using a one trial step-down IA task. DARPP-32 (dopamine and cAMP regulated phosphoprotein of Mr 32 kDa) is a cytosolic protein that is selectively enriched in medium spiny neurons in the neostriatum. It has been shown that activation of DARPP-32 and the resultant inhibition of PP-1 activity is critical for the expression of two opposing forms of brain synaptic plasticity, striatal LTD and LTP. Both forms of plasticity are also critically linked to the activation of DA receptors. It has been shown with studies in DARPP-32 KO mice an important role of this protein in mediating the effects of DA on long term changes in neuronal excitability and to our knowledge, no studies have examined the effect of IA task on DARPP-32 expression. In order to demonstrate changes in the protein expression profile we analyzed DARPP-32 levels in the striatum, prefrontal cortex (PFC), hippocampus and entorhinal cortex of Wistar rats after step-down IA learning. Our results showed that IA induced changes on DARPP-32 expression in striatum and hippocampus. DARPP-32 expression changes corroborate with changes in expression and phosphorylation of CREB, NMDA, AMPA after IA that has been reported. These changes suggest that DARPP-32 might play a central role in the IA, as previously described as an integrator of the dopaminergic signal.