Pakistan Journal of Biological Sciences1028-88801812-5735Asian Network for Scientific Information10.3923/pjbs.2012.871.876RamakrishnaD. SubhashM. N.1220121518Radioligand binding studies were done to investigate the effect of chronic administration of Amitriptyline on α1-adrenoceptor (α1-AR) receptor mediated response to inositol triphosphate (IP3) in rat brain. Our studies revealed a significant decrease in the densities of α1-ARs in cortex and cerebellum of rat brain after chronic administration of Amitriptyline (10 mg kg-1 b.wt.). However, there was no significant change in the affinity of [3H]prazosin to α1-ARs. Displacement studies showed that Amitriptyline has higher affinity for α1-AR with a Ki value of 182±16 nM. Significant change was observed in basal IP3 activity in cortex and cerebellum after Amitriptyline exposure. In cortex and cerebellum of experimental rats the NE (Norepinephrine) stimulated IP3 activity was significantly decreased (1460±102 DPM/g tissue; p<0.0001; 1188±112 DPM/g tissue; p<0.0001), when compared to NE stimulated IP3 activity (4152±286 and 3952±245 DPM/g tissue, respectively) in control rats. The decrease in NE stimulated IP3 activity in both regions may be due to the significant downregulation of α1-ARs in cortex after Amitriptyline exposure as these sites are positively coupled to IP3. The observed significant decrease in α1-ARs with concomitant decrease in NE stimulated IP3 activity, after Amitriptyline treatment, suggests that Amitriptyline which has high affinity for these sites, acts by modulating the α1-AR receptor mediated response in brain.]]>Beasley, C.M., D.N. Masica and J.H. Potvin,1992107110Berridge, M.J. and R.F. Irvine,1989341197205Chuang, D.M.,19892971110Creese, I. and S.H. Snyder,19783H-Spiroperidol labels serotonin receptors in rat cerebral cortex and hippocampus.]]>49201202Devaki, R., S.S. Rao and S.M. Nadgir,200631246252Garcia-Sevilla, J.A. and J.K. Zubieta,198689673683Han, C., P.W. Abel and K.P. Minneman,19871-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle.]]>329333335Harrison, J.K., W.R. Pearson and K.R. Lynch,1991126267Hyttel, J., J.B. Nielsen and G. Nowak,1992Ex vivo radioreceptor binding studies).]]>896169Leucht, C., M. Huhn and S. Leucht,20122012Lowry, O.H., N.J. Rosebrough, A.L. Farr and R.J. Randall,1951193265275McPherson, G.A.,198317107113Mizuta, T. and T. Segawa,198950315326Newman, M.E., D. Drummer and B. Lerer,1990256826831Nojimoto, F.D., A. Mueller, F. Hebeler-Barbosa, J. Akinaga, V. Lima, L.R. Kiguti and A.S. Pupo, 2010594957Odagaki, Y., T. Koyama and I. Yamashita,1991868596Pacheco, M.A., C. Stockmeier, H.Y. Meltzer, J.C. Overholser, G.E. Dilley and R.S. Jope,1996phosphoinositide signaling and G-protein levels in depressed suicide brain.]]>7233745Palacios, J.M., D. Hoyer and R. Cortes,19874196575Ramakrishna, D. and M.N. Subhash,20102010Ressler, K.J. and C.B. Nemeroff,19994612191233Subhash, M.N. and S. Jagadeesh,19972210951099Vila, E., J. Salles and A. Badia,199082205212Wong, D.T., P.G. Threlkeld and D.W. Robertson,199154347Yamaoka, K., T. Nanba and S. Nomura,198871165175