Original Research ARTICLE

Front. Psychiatry, 08 June 2011 | http://dx.doi.org/10.3389/fpsyt.2011.00034

Combined norepinephrine/serotonergic reuptake inhibition: effects on maternal behavior, aggression, and oxytocin in the rat

Elizabeth Thomas Cox1, Thomas Merryfield Jarrett1,2, Matthew Stephen McMurray3, Kevin Greenhill4, Vivian E. Hofler4, Sarah Kaye Williams1, Paul Wayland Joyner5, Christopher L. Middleton6, Cheryl H. Walker4 and Josephine M. Johns1,3,4*
  • 1 Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 2 School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 3 Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 4 Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 5 Department of Surgery, University of Connecticut, Farmington, CT, USA
  • 6 Department of Neurosurgery, Medical College of Georgia, Augusta, GA, USA

Background: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior (MB), although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent MB in rodents indicated significant alterations in postpartum maternal care, aggression, and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on MB, aggression, and oxytocin system changes. Methods: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. MB and postpartum aggression were assessed on postpartum days 1 and 6 respectively. Oxytocin levels were measured in relevant brain regions on postpartum day 7. Predictions were that amitriptyline would decrease MB and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. Results: Amitriptyline and desipramine differentially reduced MB, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in maternal care.

Keywords: amitriptyline, desipramine, norepinephrine, serotonin, oxytocin, maternal behavior

Citation: Cox ET, Jarrett TM, McMurray MS, Greenhill K, Hofler VE, Williams SK, Joyner PW, Middleton CL, Walker CH and Johns JM (2011) Combined norepinephrine/serotonergic reuptake inhibition: effects on maternal behavior, aggression, and oxytocin in the rat. Front. Psychiatry 2:34. doi: 10.3389/fpsyt.2011.00034

Received: 18 February 2011; Accepted: 26 May 2011;
Published online: 08 June 2011.

Edited by:

Joan Irene Morrell, Rutgers, The State University of New Jersey, USA

Reviewed by:

Rina Eiden, University at Buffalo, USA
Elizabeth Mccone Byrnes, Tufts University Cummings School of Veterinary Medicine, USA
Katharine Seip, The Rockefeller University, USA

Copyright: © 2011 Cox, Jarrett, McMurray, Greenhill, Hofler, Williams, Joyner, Middleton, Walker and Johns. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Josephine M. Johns, Department of Psychiatry, The University of North Carolina at Chapel Hill, CB# 7096, Chapel Hill, NC 27599-7096, USA. e-mail: jjohns@med.unc.edu