Brain Research Bulletin 75 (2008) 545–555 Research report Chronic buspirone treatment normalizes open field behavior in olfactory bulbectomized rats: Assessment with a quantitative autoradiographic evaluation of the 5-HT 1A binding sites  Hiroki Sato a,1 , Ivan Skelin a , Guy Debonnel b, , Mirko Diksic a,c,∗ a Cone Neurological Research Laboratory, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada b Department of Psychiatry, McGill University, Montreal, QC, Canada c Faculty of Medicine, TheJ.J. Strossmayer University, Osijek, Croatia Received 17 September 2007; accepted 18 September 2007 Available online 11 October 2007 Abstract The olfactory bulbectomized (OBX) rat model of depression has been widely used in studies on the behavioral and neurochemical aspects of human depression. The objective of the present investigation was to assess open field (OF) activity and the brain regional 5-HT 1A receptor densities of the sham operated (SHX) and OBX rats treated with saline (SHX-SAL, OBX-SAL), and either 10 mg/(kg day) (SHX-B10, OBX-B10) or 20 mg/(kg day) (SHX-B20, OBX-B20) of buspirone for 14 days, delivered by a subcutaneous osmotic minipump. Adult Sprague–Dawley rats were used for this experiment. The surgery was performed on the first day of the experiment and the rats were randomly assigned to either the SHX or OBX groups. The results of the OF tests were organized in eight groups. Following 14 days of treatment and the final OF tests, the rats were sacrificed and the brains were used for 5-HT 1A receptor autoradiography using [ 3 H]8-OH-DPAT. The data showed that the OF activities, 14 days following surgery, in the OBX rats were significantly elevated when compared to the SHX rats. In the OBX rats, only the 14-day treatment with 20mg/(kgday) of buspirone normalized the elevated OF activity, the same dose shown previously to be needed for the normalization of the regional 5-HT synthesis. A significant reduction in the number of 5-HT 1A receptor sites was found in most brain regions in the OBX rats when compared to the SHX rats. Data also show that the regional density of the 5-HT 1A receptors in OBX-SAL treated rats is lower than that of the SHX-SAL rats. The 14-day treatment with either 10 or 20 mg/(kg day) of buspirone reduced the 5-HT 1A receptors in most brain regions of the SHX rats, without an obvious dose-dependent effect of the buspirone. The comparison between the OBX-B20 and control (SHX-B20) rats suggests that the buspirone treatment resulted in a regional balance in the 5-HT 1A sites. A dose dependent reduction in the density of 5-HT 1A sites was observed in the sham rats, but the buspirone treatment had very little effect on the density of the 5-HT 1A receptors in the OBX rats. From these observations, we conclude that the antidepressant effects of buspirone in the OBX rat model of depression are likely mediated through the fine tuning of the regional imbalance of 5-HT 1A receptors with even increases of about 20% in some limbic regions. The data suggest that the neurochemical effects of antidepressants should be studied in animal models of depression rather than in normal rats. © 2007 Elsevier Inc. All rights reserved. Keywords: Olfactory bulbectomy; Buspirone; Open field; 5-HT 1A receptor; Autoradiography  Presented, in part, at the 36th Annual Meeting of SFN, Atlanta, GA, 14–18 October 2006. ∗ Corresponding author at: Montreal Neurological Institute, McGill Univer- sity, 3801 University St., Montreal, QC H3A2B4, Canada. Tel.: +1 514 398 8526; fax: +1 514 398 8195. E-mail address: Mirko.diksic@mcgill.ca (M. Diksic). 1 Permanent address: Department of Neurosurgery, University of Yamanashi, 1110 Shimokato Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.  In memoriam (1949–2006). 1. Introduction Buspirone was originally developed as an antipsychotic drug, showing antagonistic effects on the presynaptic D2 receptors with anxiolytic and antidepressant properties [39,45]. Buspirone is a partial agonist on the 5-HT 1A receptor [20]. This means that with high extracellular availability of serotonin, buspirone would exert antagonistic action on 5-HT 1A receptors, while with low serotonin availability, it would act as an agonist [54]. One should keep in mind that buspirone has a pharmacologically 0361-9230/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2007.09.005