1. ¹Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany
2. ²Solvay Pharmaceuticals Research Laboratories, C.J. van Houtenlaan, Weesp, The Netherlands

Correspondence: Dr B Czeh, Clinical Neurobiology Laboratory, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany. Tel: +49 551 3851 134; Fax: +49 551 3851 307; E-mail: bczeh@dpz.gwdg.de

Received 20 January 2004; Revised 3 July 2004; Accepted 9 August 2004; Published online 0 September 2004.

Abstract

Previous studies have demonstrated that stress may affect the hippocampal GABAergic system. Here, we examined whether long-term psychosocial stress influenced the number of parvalbumin-containing GABAergic cells, known to provide the most powerful inhibitory input to the perisomatic region of principal cells. Adult male tree shrews were submitted to 5 weeks of stress, after which immunocytochemical and quantitative stereological techniques were used to estimate the total number of hippocampal parvalbumin-immunoreactive (PV-IR) neurons. Stress significantly decreased the number of PV-IR cells in the dentate gyrus (DG) (-33%), CA2 (-28%), and CA3 (-29%), whereas the CA1 was not affected. Additionally, we examined whether antidepressant treatment offered protection from this stress-induced effect. We administered fluoxetine (15 mg/kg per day) and SLV-323 (20 mg/kg per day), a novel neurokinin 1 receptor (NK₁R) antagonist, because the NK₁R has been proposed as a possible target for novel antidepressant therapies. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of the drugs, with stress continued throughout the 28-day treatment period. NK₁R antagonist administration completely prevented the stress-induced reduction of the number of PV-IR interneurons, whereas fluoxetine attenuated this decrement in the DG, without affecting the CA2 and CA3. The effect of stress on interneuron numbers may reflect real cell loss; alternatively, parvalbumin concentration is diminished in the neurons, which might indicate a compensatory attempt. In either case, antidepressant treatment offered protection from the effect of stress and appears to modulate the hippocampal GABAergic system. Furthermore, the NK₁R antagonist SLV-323 showed neurobiological efficacy similar to that of fluoxetine.