The conditioned taste aversion (CTA) paradigm can be applied to study associative learning in rats and evaluate the molecular mechanisms that underpin this process. This study examined the role of Extracellular signal Regulated kinase (pERK) in acquisition and expression phases of lithium-elicited CTA. Moreover, since a complex interplay links activation of ERK and DARPP-32, DARPP-32 phosphorylation pattern was also studied. Rats, trained to drink water daily over a restricted period of time, once reached a stable fluid intake were exposed to sucrose solution and one hour later were administered lithium (125 mg/kg i. p.) or saline (CTA acquisition). On the test day, lithium-conditioned rats avoided drinking the sucrose solution (CTA expression). CTA acquisition was associated with an increase in pERK-positive neurons in the mPFCx and BSTL, and CTA expression with an increase in pERK-positive neurons in the AcbSh and AcbC, compared to control rats. DARPP-32 phosphorylation pattern remained unmodified during both expression and acquisition phases. Furthermore, using immunogold electron microscopy, we investigated the subcellular localization of pERK signal in the AcbSh of lithium-conditioned and control rats from the expression group. Ultrastructural analysis of post-embedding immunogold labeling revealed a strong pERK signal inside the nucleus and, to a lesser extent, in the perinuclear cytoplasm and dendritic processes. In addition, Golgi-Cox analysis revealed a significant increase of dendritic spines density in AcbSh neurons of lithium-conditioned rats compared with controls. These results indicate that pERK is differentially activated during acquisition and expression of the aversive association in distinct brain structures and that this activation during CTA expression parallels significant changes in dendritic spines density.
CONDITIONED TASTE AVERSION ELICITED ERK ACTIVATION AND CHANGES OF DENDRITIC SPINES DENSITY: AN IMMUNOHISTOCHEMICAL, GOLGI-COX AND ELECTRON MICROSCOPY STUDY
ACQUAS, ELIO MARIA GIOACHINO;FENU, SANDRO;
2011-01-01
Abstract
The conditioned taste aversion (CTA) paradigm can be applied to study associative learning in rats and evaluate the molecular mechanisms that underpin this process. This study examined the role of Extracellular signal Regulated kinase (pERK) in acquisition and expression phases of lithium-elicited CTA. Moreover, since a complex interplay links activation of ERK and DARPP-32, DARPP-32 phosphorylation pattern was also studied. Rats, trained to drink water daily over a restricted period of time, once reached a stable fluid intake were exposed to sucrose solution and one hour later were administered lithium (125 mg/kg i. p.) or saline (CTA acquisition). On the test day, lithium-conditioned rats avoided drinking the sucrose solution (CTA expression). CTA acquisition was associated with an increase in pERK-positive neurons in the mPFCx and BSTL, and CTA expression with an increase in pERK-positive neurons in the AcbSh and AcbC, compared to control rats. DARPP-32 phosphorylation pattern remained unmodified during both expression and acquisition phases. Furthermore, using immunogold electron microscopy, we investigated the subcellular localization of pERK signal in the AcbSh of lithium-conditioned and control rats from the expression group. Ultrastructural analysis of post-embedding immunogold labeling revealed a strong pERK signal inside the nucleus and, to a lesser extent, in the perinuclear cytoplasm and dendritic processes. In addition, Golgi-Cox analysis revealed a significant increase of dendritic spines density in AcbSh neurons of lithium-conditioned rats compared with controls. These results indicate that pERK is differentially activated during acquisition and expression of the aversive association in distinct brain structures and that this activation during CTA expression parallels significant changes in dendritic spines density.
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