Dissociation of the effect of spatial behaviors on the phosphorylation of cAMP-response element binding protein (CREB) within the nucleus accumbens

Several studies have reported a role for the nucleus accumbens (NAcc) in learning and synaptic plasticity. Many of them suggest that the NAcc is involved in translating cortico-limbic information to the motor system mediating spatial learning and memory processes. Previous studies from our laboratory have shown that protein kinase C is activated following training in a food search spatial learning task. The present study further characterizes the molecular substrates associated with NAcc-dependent spatial behavior. The cyclic AMP-response element binding protein (CREB), a transcription factor implicated in the formation of long-term memory, was studied in the NAcc following spatial training in a food search spatial learning task. Western blots were performed to detect phosphorylated (activated) and total CREB protein levels. Our results show that CREB is significantly phosphorylated in the NAcc 48 h after habituation and at 5 min and 1 h after the first spatial training session in comparison with the naive animals that remained in their home cages. Since published data show that NAcc plays a role in novelty detection and reactivity, we conducted further experiments in order to dissociate the effect on CREB phosphorylation and expression of spatial novelty (single exposure), exploration, and spatial learning in the food search apparatus. Results show that CREB phosphorylation is significantly increased 48 h after exposure to a novel environment. The present study suggests that CREB phosphorylation observed in the NAcc during habituation and spatial training may be mainly triggered by detection of spatial novelty.