Acute dehydroepiandrosterone treatment exerts different effects on dopamine and serotonin turnover ratios in the rat corpus striatum and nucleus accumbens Iván Pérez-Neri, Israel Méndez-Sánchez, Sergio Montes, Camilo Ríos ⁎ Department of Neurochemistry, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, La Fama, Tlalpan, Mexico City 14269, Mexico ABSTRACT ARTICLE INFO Article history: Received 6 February 2008 Received in revised form 5 June 2008 Accepted 5 June 2008 Available online 10 June 2008 Keywords: Depression Monoamine oxidase Neuroprotection It has been shown that the steroid dehydroepiandrosterone (DHEA) interacts with dopamine (DA) and serotonin (5-HT) neurotransmitter systems, which are involved in the pathophysiology of neurological and psychiatric diseases such as Parkinson's disease as well as mood and psychotic disorders. To explore if DHEA modulates DA and 5-HT metabolism we analyzed the content of both neurotransmitters and their metabolites in the rat corpus striatum (CS) and nucleus accumbens (NAc) 2 h after steroid administration (30, 60 and 120 mg/kg i.p.). DHEA treatment significantly reduced DA turnover (up to 33%) in the CS, but increased 5-HT turnover (up to 76%) in both regions. Those effects could be relevant to mood and neurodegenerative disorders. © 2008 Elsevier Inc. All rights reserved. 1. Introduction It has been shown that dehydroepiandrosterone (DHEA) mod- ulates several neurotransmitter systems and this might be involved in its behavioral effects (Pérez-Neri et al., 2008). Regarding monoamines, some studies suggest that DHEA and its sulfated ester (dehydroepian- drosterone sulfate, DHEAS) may reduce dopamine (DA) D2 receptor activation (Catalina et al., 2002; Suárez et al., 2005), while DHEAS increases D1 receptor-dependent PKA activity (Dong et al., 2007). Also, both DHEA and DHEAS increase DA release from cell cultures (Charalampopoulos et al., 2005; Murray and Gillies, 1997). Some studies show that DHEA administration alters both DA and serotonin (5-HT) metabolism in the hypothalamus (Catalina et al., 2001; Gillen et al., 1999; Pham et al., 2000; Porter et al., 2005) while other studies did not find significant effects on DA metabolism in other brain regions such as the corpus striatum (CS) and midbrain (Nguyen et al., 1999). A previous study showed that the intrastriatal injection of DHEA reduces 3,4-dihydroxyphenylacetic acid (DOPAC) content in the CS, suggesting reduced monoamine oxidase (MAO) activity, which might be involved in the neuroprotective effect of DHEA in experimental models of Parkinson's disease (PD) (Tomas-Camardiel et al., 2002). In the present study we explore the acute effect of DHEA administration on the content of DA, 5-HT and their metabolites in Progress in Neuro-Psychopharmacology & Biological Psychiatry 32 (2008) 1584–1589 Abbreviations: 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin; CS, corpus striatum; DA, dopamine; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandros- terone sulfate; DOPAC, 3,4-dihydroxyphenylacetic acid; HPLC, high-performance liquid chromatography; HVA, homovanillic acid; MAO, monoamine oxidase; MAOI, MAO inhibitor; NAc, nucleus accumbens; PD, Parkinson's disease. ⁎ Corresponding author. Tel.: +52 55 56063822; fax: +52 55 54240808. E-mail address: crios@correo.xoc.uam.mx (C. Ríos). the CS and the nucleus accumbens (NAc) to study the modulation of monoamine metabolism in the main dopaminoceptive nuclei in the rat brain. 2. Materials and methods 2.1. Chemicals DA, DOPAC, 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid, HVA), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), trans-DHEA and sodium octyl sulfate were obtained from Sigma (St. Louis, MO, USA). HPLC-grade absolute methanol was obtained from Mallinckrodt Baker (Mexico). All other reagents were analytical grade. 2.2. Animals, treatments and sample processing DHEA was dissolved in propylene glycol and injected [30 (n = 8), 60 (n =6) and 120 (n = 6) mg/kg, i.p.)] to male Wistar rats weighing 200– 250 g. Control animals (n =10) received an equivalent volume of the vehicle. DHEA doses were selected to cover a wide range used in previous studies; also, the selection of the vehicle, the administration route and the time for sacrifice after treatment were selected according to those studies (Gillen et al., 1999; Nguyen et al., 1999; Pham et al., 2000; Porter et al., 2005). Two hours after steroid administration animals were sacrificed by decapitation; the whole CS and NAc were dissected out and stored at - 70 °C. The day of analysis, samples were thawed and homogenized in 0.4 N perchloric acid containing 0.1% sodium metabisulfite as previously reported (Montes et al., 2001). Homogenates were centrifuged at 18,500× g at 4°C for 15 min and supernatants were kept on ice during analysis. Experiments were carried out according to the 0278-5846/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2008.06.002 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnpbp