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Molecular and behavioral characterization of adolescent protein kinase C following high dose ethanol exposure

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Abstract

Rationale

Ethanol is commonly used and abused during adolescence. Although adolescents display differential behavioral responses to ethanol, the mechanisms by which this occurs are not known. The protein kinase C (PKC) pathway has been implicated in mediating many ethanol-related effects in adults, as well as gamma-aminobutyric acid (GABAA) receptor regulation.

Objectives

The present study was designed to characterize cortical PKC isoform and GABAA receptor subunit expression during adolescence relative to adults as well as assess PKC involvement in ethanol action.

Results

Novel PKC isoforms were elevated, while PKCγ was lower during mid-adolescence relative to adults. Whole-cell lysate and synaptosomal preparations correlated for all isoforms except PKCδ. In parallel, synaptosomal GABAA receptor subunit expression was also developmentally regulated, with GABAAR δ and α4 being lower while α1 and γ2 were higher or similar, respectively, in adolescents compared to adults. Following acute ethanol exposure, synaptosomal novel and atypical PKC isoform expression was decreased only in adolescents. Behaviorally, inhibiting PKC with calphostin C, significantly increased ethanol-induced loss of righting reflex (LORR) in adolescents but not adults, whereas activating PKC with phorbol dibutyrate was ineffective in adolescents but decreased LORR duration in adults. Further investigation revealed that inhibiting the cytosolic phospholipase A2/arachidonic acid (cPLA2/AA) pathway increased LORR duration in adolescents, but was ineffective in adults.

Conclusions

These data indicate that PKC isoforms are variably regulated during adolescence and may contribute to adolescent ethanol-related behavior. Furthermore, age-related differences in the cPLA2/AA pathway may contribute to ethanol’s age-related effects on novel and atypical PKC isoform expression and behavior.

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Abbreviations

AA:

arachidonic acid

cPLA2 :

cytoplasmic phospholipase A2

GABA:

gamma-aminobutyric acid

GABAAR:

GABA type A receptor

PKC:

protein kinase C

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Acknowledgments

This work was supported by the National Institute of Health grants AA017823 and AA019367 and the Developmental Exposure Alcohol Research Center. The authors would like to thank Laura Mickelson for her technical assistance. We would also like to thank Linda Spear and A. Leslie Morrow for their thoughtful comments and discussions during the drafting of this manuscript.

Conflict of interest

The authors have no financial conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA

    Jessica L. Santerre, Eduardo D. Gigante, Justine D. Landin & David F. Werner

  2. Center for Development and Behavioral Neuroscience, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA

    Jessica L. Santerre, Eduardo D. Gigante, Justine D. Landin & David F. Werner

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  1. Jessica L. Santerre
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  2. Eduardo D. Gigante
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  3. Justine D. Landin
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  4. David F. Werner
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Correspondence to David F. Werner.

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Santerre, J.L., Gigante, E.D., Landin, J.D. et al. Molecular and behavioral characterization of adolescent protein kinase C following high dose ethanol exposure. Psychopharmacology 231, 1809–1820 (2014). https://doi.org/10.1007/s00213-013-3267-6

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  • DOI: https://doi.org/10.1007/s00213-013-3267-6

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