European Neuropsychopharmacology 10 (1999) 21–26 www.elsevier.com / locate / euroneuro 3 Distribution and characterization of [ H]mesulergine binding in human brain postmortem * Donatella Marazziti , Alessandra Rossi, Gino Giannaccini, Katia M. Zavaglia, Liliana Dell’Osso, Antonio Lucacchini, Giovanni B. Cassano Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Via Roma, 67, 56100 Pisa, Italy Received 22 March 1999; accepted 12 July 1999 Abstract Much interest is currently being directed towards serotonin (5-HT) receptors of type 2C (5-HT ) because of their possible 2C involvement in the control of different activities, such as the composition of the cerebrospinal fluid, locomotion, feeding, neuronal excitability and anxiety. The limited information regarding their distribution in the human brain prompted us to investigate, and to 3 characterize the binding of [ H]mesulergine, a HT antagonist, in autopsy samples from 24 subjects. 2C 3 The results showed that the [ H]mesulergine binding represented 95% of the total binding and equilibrium saturation binding experiments resulted in a single straight line, consistent with the presence of one site only. The area with the highest density of 3 [ H]mesulergine binding was the choroid plexus, followed at a significantly lower level by the hippocampus, substantia nigra, basal 3 ganglia, amygdala, hypothalamus and prefrontal cortex. The pharmacological profile of the [ H]mesulergine binding was consistent with that of 5-HT receptors, since the most effective displacers were ritanserin, mesulergine and mianserine, followed by clozapine, 2C ketanserine and m-CPP, while other compounds had a negligible or no effect. 3 These findings, showing a wide distribution of [ H]mesulergine binding sites in the human brain, could provide anatomical bases for the different functions attributable to 5-HT receptors in humans.  1999 Elsevier Science B.V. All rights reserved. 2C 3 Keywords: Serotonin; Serotonin receptors; Serotonin receptors of type 2C; Human brain; [ H]Mesulergine; Pharmacological characterization 1. Introduction mainly on the epithelial cells of the choroid plexus (Pazos and Palacios, 1985; Yagaloff and Hartig, 1985); as a result, Serotonin (5-HT) receptors of type 2 (5-HT ) are it has been hypothesized that they might regulate the 2 currently classified as 5-HT and 5-HT subtypes (Zifa composition and volume of the cerebrospinal fluid (Pazos 2A 2C and Fillion, 1992; Hoyer and Martin, 1997). The 5-HT et al., 1985; Kaufman et al., 1995). 2C receptors were initially considered to belong to class 1 In addition to the choroid plexus, 5-HT receptors have 2C because of their high affinity for 5-HT and they were been identified in human basal ganglia, in particular the named 5-HT (Pazos et al., 1984; Hartig, 1989); how- substantia nigra, globus pallidus and caudate, by means of 1C ever, their recognitory and transductory properties and autoradiographic techniques (Pazos et al., 1987), and in rat their subsequent cloning and comparison of nucleotide limbic structures, such as the cingulate cortex, habenula sequences showed clear similarities with the 5-HT family and olfactory nucleus, with in-situ hybridization studies 2 (Lubbert et al., 1987; Julius et al., 1988; Hoyer et al., (Mengod et al. 1990; Wright et al., 1995; Eberle-Wang et 1989; Saltzman et al., 1991; Baxter et al., 1995). al., 1997) or specific antisera (Abramowski et al., 1995). The 5-HT receptors appear to be quite similar in all Although some of the functions traditionally attributed 2C mammalian species, including man, and have been found to 5-HT receptors may, in fact, be due to the 5-HT 2A 2C subtypes, the question is made difficult to resolve mainly by the lack of selective agonists or antagonists interacting *Corresponding author. Tel.: 139-50-835-412; fax: 139-50-21581. E-mail address: dmarazzi@psico.med.unipi.it (D. Marazziti) with them. 0924-977X / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S0924-977X(99)00045-0