Antidepressant binding sites in brain: autoradiographic comparison of [3H]paroxetine and [3H]imipramine localization and relationship to serotonin transporter

PD Hrdina, B Foy, A Hepner and RJ Summers

Department of Pharmacology, University of Ottawa, Ontario, Canada.

Binding of two different antidepressant drugs, [3H]paroxetine and [3H]imipramine in 30 rat brain regions was visualized, compared and quantified by means of autoradiography and densitometry. Specific binding of [3H]paroxetine to coronal sections of diencephalon represented 85% of total binding and was saturable and of high affinity (KD, 0.36 +/- 0.07 nM) with a maximum number of binding sites of 276 +/- 41 fmol/mg protein. The autoradiograms showed a heterogenous distribution of [3H]paroxetine in brain with selective accumulation of label in brain regions known to contain serotonergic terminals, axons and cell bodies (amygdaloid and raphe nuclei, superior colliculus, substantia nigra and medial forebrain bundle). Binding was displaced selectively with other serotonin uptake inhibitors (clomipramine and fluoxetine) and almost abolished by lesioning the serotonergic neurons with p-chloroamphetamine. The desipramine-sensitive [3H]imipramine binding was more diffuse with relatively high density in cerebral cortex and hippocampus and was only decreased partially in animals treated with p-chloroamphetamine. The results indicate that [3H]paroxetine, but not [3H]imipramine, is a ligand of choice to selectively label serotonergic structures in brain.

Volume 252, Issue 1, pp. 410-418, 01/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				M. S. Ansorge, M. Zhou, A. Lira, R. Hen, and J. A. Gingrich Early-Life Blockade of the 5-HT Transporter Alters Emotional Behavior in Adult Mice Science, October 29, 2004; 306(5697): 879 - 881. [Abstract] [Full Text] [PDF]

				T. Frodl, E. M. Meisenzahl, P. Zill, T. Baghai, D. Rujescu, G. Leinsinger, R. Bottlender, C. Schule, P. Zwanzger, R. R. Engel, et al. Reduced Hippocampal Volumes Associated With the Long Variant of the Serotonin Transporter Polymorphism in Major Depression Arch Gen Psychiatry, February 1, 2004; 61(2): 177 - 183. [Abstract] [Full Text] [PDF]

				Q. Li, L. Ma, R. B. Innis, N. Seneca, M. Ichise, H. Huang, M. Laruelle, and D. L. Murphy Pharmacological and Genetic Characterization of Two Selective Serotonin Transporter Ligands: 2-[2-(Dimethylaminomethylphenylthio)]-5-fluoromethylphenylamine (AFM) and 3-Amino-4-[2-(dimethylaminomethyl-phenylthio)]benzonitrile (DASB) J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 481 - 486. [Abstract] [Full Text] [PDF]

				A. Androutsellis-Theotokis, N. R. Goldberg, K. Ueda, T. Beppu, M. L. Beckman, S. Das, J. A. Javitch, and G. Rudnick Characterization of a Functional Bacterial Homologue of Sodium-dependent Neurotransmitter Transporters J. Biol. Chem., April 4, 2003; 278(15): 12703 - 12709. [Abstract] [Full Text] [PDF]

				S. Chalon, J. Tarkiainen, L. Garreau, H. Hall, P. Emond, J. Vercouillie, L. Farde, P. Dasse, K. Varnas, J.-C. Besnard, et al. Pharmacological Characterization of N,N-Dimethyl-2-(2-amino-4-methylphenyl thio)benzylamine as a Ligand of the Serotonin Transporter with High Affinity and Selectivity J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 81 - 87. [Abstract] [Full Text] [PDF]

				G. Pineyro and P. Blier Autoregulation of Serotonin Neurons: Role in Antidepressant Drug Action Pharmacol. Rev., September 1, 1999; 51(3): 533 - 591. [Abstract] [Full Text] [PDF]

				X. Li, D. G. Rainnie, R. W. McCarley, and R. W. Greene Presynaptic Nicotinic Receptors Facilitate Monoaminergic Transmission J. Neurosci., March 1, 1998; 18(5): 1904 - 1912. [Abstract] [Full Text] [PDF]

				G. A. Ordway, C. A. Stockmeier, G. W. Cason, and V. Klimek Pharmacology and Distribution of Norepinephrine Transporters in the Human Locus Coeruleus and Raphe Nuclei J. Neurosci., March 1, 1997; 17(5): 1710 - 1719. [Abstract] [Full Text] [PDF]