Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

Roberto Marotta; Sandro Fenu; Simona Scheggi; Stefania Vinci; Michela Rosas; Andrea Falqui; Carla Gambarana; M Graziella De Montis; Elio Acquas

doi:10.3389/fnbeh.2014.00153

Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

Front Behav Neurosci. 2014 May 7:8:153. doi: 10.3389/fnbeh.2014.00153. eCollection 2014.

Authors

Roberto Marotta¹, Sandro Fenu², Simona Scheggi³, Stefania Vinci⁴, Michela Rosas⁵, Andrea Falqui¹, Carla Gambarana³, M Graziella De Montis³, Elio Acquas²

Affiliations

¹ EM Laboratory, Department of Nanochemistry, Istituto Italiano di Tecnologia - IIT Genova, Italy.
² Department of Toxicology, University of Cagliari Cagliari, Italy ; Centre of Excellence on Neurobiology of Addiction, University of Cagliari Cagliari, Italy ; National Institute of Neuroscience - INN, University of Cagliari Cagliari, Italy.
³ Department of Neuroscience, University of Siena Siena, Italy.
⁴ Department of Toxicology, University of Cagliari Cagliari, Italy.
⁵ Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.

Abstract

Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr(34)- and Thr(75-Dopamine-and-cAMP-Regulated) PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr(34)- and p-Thr(75)-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr(34)- and p-Thr(75-DARPP-32) levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.

Keywords: conditioned taste aversion (CTA); extracellular signal regulated kinase (ERK); glutamate receptors; immuno electron microscopy; nucleus accumbens (Acb); prefrontal cortex (PFCx).