Psychopharmacology

, Volume 183, Issue 4, pp 404–412 | Cite as

Desipramine attenuates working memory impairments induced by partial loss of catecholamines in the rat medial prefrontal cortex

Original Investigation
First Online:
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Accepted:

Abstract

Rationale

The density of tyrosine hydroxylase-immunoreactive (TH-IR) axons in the prefrontal cortex of schizophrenic subjects may be reduced by as much as 50% in the deep cortical layers (Am J Psychiatry 156:1580–1589, 1999). Previously, we demonstrated that ~60% loss of TH-IR axons in the rat medial prefrontal cortex (mPFC) decreases local basal and stress-evoked extracellular dopamine (DA) concentrations, suggesting that moderate loss of DA axons in the mPFC is sufficient to alter the neurochemical activity of the remaining DA neurons (Neuroscience 93:497–505, 1999).

Objectives

To further assess the functional consequences of partial mPFC DA depletion, we examined the effects of 6-hydroxydopamine lesions of the rat mPFC on behavior in a T-maze delayed-response task. We also assessed whether chronic administration of the norepinephrine (NE) uptake inhibitor, desipramine (DMI), attenuates lesion-induced deficits in T-maze performance. Previous research indicates that inhibition of NE transport in the mPFC results in a concomitant increase in extracellular DA and NE.

Results

Moderate loss of mPFC DA and NE (~50 and 10% loss, respectively) was sufficient to impair delayed-response behavior, in part due to an increase in perseverative responding. Chronic DMI treatment (3 mg/kg delivered via osmotic pumps) impaired performance of control rats but attenuated the deficits in delayed-response behavior in rats previously sustaining loss of mPFC DA and NE (~75 and 35% loss, respectively).

Conclusion

These data suggest that moderate loss of DA and NE in the prefrontal cortex is sufficient to impair cognitive function, and these behavioral effects are attenuated by inhibition of the NE transporter.

Keywords

Norepinephrine 6-Hydroxydopamine Delayed response T-maze 
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Notes

Acknowledgements

This work was supported by USPHS grants MH45156 and MH61616 and a Summer Research Grant from WWU Bureau for Faculty Research.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • S. M. Clinton
    • 1
  • I. L. Sucharski
    • 2
  • J. M. Finlay
    • 3
  1. 1.Mental Health Research Institute and Department of PsychiatryUniversity of MichiganAnn ArborUSA
  2. 2.Psychology DepartmentUniversity of DelawareNewarkUSA
  3. 3.Department of PsychologyWestern Washington UniversityBellinghamUSA

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