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Corticolimbic changes in acetylcholine and cyclic guanosine monophosphate in the Flinders Sensitive Line rat: a genetic model of depression

Published online by Cambridge University Press:  24 June 2014

Linda Brand ,
Jurgens van Zyl ,
Estella L. Minnaar ,
Francois Viljoen ,
Jan L. du Preez ,
Gregers Wegener  and
Brian H. Harvey
Linda Brand*
Affiliation:
Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
Jurgens van Zyl
Affiliation:
Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
Estella L. Minnaar
Affiliation:
Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
Francois Viljoen
Affiliation:
Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
Jan L. du Preez
Affiliation:
Analytical Technology Laboratory, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
Gregers Wegener
Affiliation:
Centre for Psychiatric Research, University of Aarhus, Denmark
Brian H. Harvey
Affiliation:
Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom, South Africa
*
Linda Brand, Division of Pharmacology, Unit for Drug Research and Development, School of Pharmacy, North-West University, 2520 Potchefstroom, South Africa. Tel: +27(18)2992233; Fax: +27(18)2992225; E-mail: [email protected]
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Extract

Objective: Depression is suggested to involve disturbances in cholinergic as well as glutamatergic pathways, particularly the N-methyl-d-aspartate receptor-mediated release of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). The aim of this study was to determine whether the Flinders Sensitive Line (FSL) rat, a genetic model of depression, presents with corticolimbic changes in basal acetylcholine (ACh) levels and NO/cGMP signalling.

Methods: Basal levels of nitrogen oxides (NOx) and both basal and l-arginine-stimulated nitric oxide synthase (NOS) formation of l-citrulline were analysed in hippocampus and frontal cortex in FSL and control Flinders resistant line (FRL) rats by fluorometric and electrochemical high-performance liquid chromatography, respectively. In addition, ACh and cGMP levels were analysed by liquid chromatography tandem mass spectrometry and radioimmunoassay, respectively.

Results: Significantly elevated frontal cortical but reduced hippocampal ACh levels were observed in FSL versus FRL rats. Basal cGMP levels were significantly reduced in the frontal cortex, but not hippocampus, of FSL rats without changes in NOx and l-citrulline, suggesting that the reduction of cGMP follows through an NOS-independent mechanism.

Conclusions: These data confirm a bidirectional change in ACh in the frontal cortex and hippocampus of the FSL rat, as well as provide evidence for a frontal cortical ACh-cGMP interaction in the depressive-like behaviour of the FSL rat.

Keywords

cGMPcholinergicFlinders Sensitive Line ratfrontal cortexhippocampusmajor depressionnitric oxide
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 4 , August 2012 , pp. 215 - 225
Copyright
Copyright © Cambridge University Press 2011

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