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Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat

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Abstract

Rationale

Mesolimbic dopamine (DA), particularly in the nucleus accumbens, importantly regulates activational aspects of maternal responsiveness. DA antagonism and accumbens DA depletions interfere with early postpartum maternal motivation by selectively affecting most forms of active maternal behaviors, while leaving nursing behavior relatively intact. Considerable evidence indicates that there is a functional interaction between DA D2 and adenosine A2A receptors in striatal areas, including the nucleus accumbens.

Objective

This study was conducted to determine if adenosine A2A receptor antagonism could reverse the effects of DA receptor antagonism on early postpartum maternal behavior.

Methods

The adenosine A2A receptor antagonist MSX-3 (0.25–2.0 mg/kg, IP) was investigated for its ability to reverse the effects of the DA D2 receptor antagonist haloperidol (0.1 mg/kg, IP) on the maternal behavior of early postpartum female rats.

Results

Haloperidol severely impaired the expression of active maternal components, including retrieval and grouping the pups at the nest site, pup licking, and nest building. Co-administration of MSX-3 (0.25–2.0 mg/kg, IP) with haloperidol produced a dose-related attenuation of the haloperidol-induced behavioral deficits in early postpartum females. Doses of MSX-3 that effectively reversed the effects of haloperidol (0.5, 1.0 mg/kg), when administered in the absence of haloperidol, did not affect maternal responding or locomotor activity.

Conclusions

Adenosine and DA systems interact to regulate early postpartum maternal responsiveness. This research may potentially contribute to the development of strategies for treatments of psychiatric disorders during the postpartum period, with particular emphasis in maintaining or restoring the mother–infant relationship.

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Acknowledgements

This research was supported by NARSAD Young Investigator Award and NIH SOAR DA027945 awarded to MP, NIMH MH078023 awarded to JDS, and NIH DA014025 awarded to JIM. The authors thank the Laboratory Animal Facility staff at Rutgers University, Newark Campus, for animal breeding and care.

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Authors and Affiliations

  1. Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, NJ, 07102, USA

    Mariana Pereira, Andrew M. Farrar & Joan I. Morrell

  2. Department of Psychology, Division of Behavioral Neuroscience, University of Connecticut, Storrs, CT, 06269-1020, USA

    John D. Salamone

  3. Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie I, Universität Bonn, Bonn, Germany

    Jörg Hockemeyer & Christa E. Müller

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  1. Mariana Pereira
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Correspondence to Mariana Pereira.

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Pereira, M., Farrar, A.M., Hockemeyer, J. et al. Effect of the adenosine A2A receptor antagonist MSX-3 on motivational disruptions of maternal behavior induced by dopamine antagonism in the early postpartum rat. Psychopharmacology 213, 69–79 (2011). https://doi.org/10.1007/s00213-010-2015-4

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