Molecular neuropsychopharmacology S25 several specific brain regions are responsible for mediating the therapeutic effect. Here, electrical stimulation was delivered to a key region in the brain reward system, the nucleus accumbens (NAc), in a rat model for depression in order to measure behavioral and some neurochemical outcomes of such repeated localized stimulation. Methods: An electrode was implanted into the left NAc of male Sprague-Dawley rats. Then, rats were exposed to the chronic mild stress (CMS) paradigm (Willner, 2005), which induce several depressive symptoms in our setup. Then, 10 daily sessions of subconvulsive electrical stimulation (SCES) of the NAc, were applied using frequencies and patterns parallel to those in human transcranial magnetic stimulation studies. For controls, implanted animals exposed to the same CMS protocol received sham stimulation. Other groups of animals received real or sham stimulation but were not exposed to the CMS procedure. The behavioral tests included sucrose preference (a measure for anhedonia), exploration (using locomotion boxes equipped with photobeems), sexual behavior and Morris water maze. Then, rats were sacrificed and punches of various brain regions were taken for measurements of brain-derived neurotrophic factor (BDNF) levels using ELISA kits. Results: While CMS induced a reduction in sucrose preference, animals that received active SCES treatment of the NAc had normal levels of sucrose preference. In addition, the number of mounts in the sexual behavior test, which was lower in CMS animals, was normalized by SCES of the NAc. Independently of the stimulation effect in the female preference test (when males were introduced to a new female rat at the same time) control animals preferred to mount more often the new female compared to their previous partner, but CMS animal did not show such preference. In the exploration test, SCES of the NAc induced an increase in rearing behavior and the number of the visits in the central area. Learning in the Morris water maze was not affected by the SCES treatment. Finally, BDNF levels were increased in the dorsal dentate gyrus and in the striatum following SCES treatment of the NAc in CMS animals. Discussion: This study suggests that SCES of the NAc normalizes depressive behaviors that are induced by CMS in animals. In addition, the SCES treatment did not impair learning and memory as indicated in the Morris water maze. BDNF levels in the dorsal dentate gyrus, previously found to be decreased in depression and increased after chronic antidepressant treatment (Smith et al. 1995, Dwivedi et al. 2003), are increased following SCES treatment of the NAc, suggesting a potential therapeutic mechanism. We anticipate that finding brain regions, such as the NAc, in which electrical stimulation enable treating depressive behavior in animals could lead to better understanding of depression and the mechanism of ECT and to development of electrical (or transcranial magnetic) brain stimulation treatment for depression in humans. Reference(s) [1] Willner P, 2005, Chronic Mild Stress (CMS) revisited: consistency and behavioural–neurobiological concor- dance in the effects of CMS. Neuropsychobiology 52, 90–110. [2] Smith MA, Makino S, Kvernansky R, et al., 1995, Stress alters the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15, 1768–1777. [3] Dwivedi Y, Rizavi HS, Conley RR, et al., 2003, Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatr 60, 804– 815. P.1.29 Effect of clozapine on dopamine D1 and D2 receptors interaction in the HEK 293 cells A. Faron-Gorecka 1 , A. G´ orecki 2 , M. Kusmider 1 , Z. Wasylewski 2 , M. Dziedzicka-Wasylewska 3 . 1 Polish Academy of Sciences, Department of Pharmacology, Krakow, Poland; 2 Jagiellonian University, Department of Physical Biochemistry, Krakow, Poland; 3 Polish Academy of Sciences Department of Pharmacology, Jagiellonian University Department of Physical Biochemistry, Krakow, Poland Clozapine belongs to so called atypical neuroleptic drugs, and with regard to the therapeutic effects, it seems to be superior to conventional antipsychotics. The precise identification of the mechanism of action of clozapine is still not clear. Clozapine, in contrast to classic neuroleptics, alleviates both positive and negative symptoms of schizophrenia and does not produce extrapyramidal syndrome or elevate prolactin levels in plasma. Dopamine D 1 and D 2 receptors have been long suggested to play a role in the pathophysiology and treatment of schizophrenia [1] and these receptors are among several central neurotransmitter receptors for which clozapine has been shown to display moderate affinity. Since endogenous dopamine has been suggested to influence the radioligand binding parameters, we report here the data concerning the affinity of clozapine for dopamine D 1 and D 2 receptors in the model system, devoid of endogenous dopamine. Similar arguments are