Morphology and distribution of neurons expressing serotonin 5-HT 1A receptors in the rat hypothalamus and the surrounding diencephalic and telencephalic areas Eric Marvin a , Karie Scrogin b , Bertalan Duda ´s a, * a Neuroendocrine Organization Laboratory (NEO), Lake Erie College of Osteopathic Medicine (LECOM), Erie, PA, United States b Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States 1. Introduction The central serotoninergic system plays a pivotal role in regulating a broad range of hypothalamic functions including cardiovascular responses, feeding, mood, circadian rhythm, neuroendocrine function and sleep (Curzon, 1990; Amir et al., 1998; Oberndorfer et al., 2000; Horiuchi et al., 2006; Jorgensen, 2007; Barabanova et al., 2007). Since numerous hypothalamic areas receive axon collaterals from serotoninergic perikarya located in the midbrain (Petrov et al., 1994; Ljubic-Thibal et al., 1999), it is a general consensus that various serotoninergic effects may be mediated via hypothalamic neurotransmitter systems. However, the distribution and morphology of the neural structures directly influenced by the serotoninergic system are not entirely known. In rat, the hypothalamic serotoninergic system is composed almost exclusively of fiber varicosities, although a small number of serotoninergic perikarya can be visualized by immunohistochem- istry in the hypothalamic dorsomedial nucleus after nialamide and L-tryptophan treatment (Steinbusch and Nieuwenhuys, 1981; Steinbusch, 1984). Since the serotoninergic fibers are scattered throughout the entire hypothalamus with the exception of the optic chiasm/tract and the fornix (Steinbusch and Nieuwenhuys, 1981; Steinbusch, 1984), it is generally believed that they influence hypothalamic neurons via synaptic connections. Indeed, previous studies described intimate associations between the serotoniner- gic axonal varicosities and other neurotransmitter systems in the human hypothalamus. Serotoninergic axon varicosities form juxtapositions with vasopressinergic hypothalamic neurons in hamster (Ferris et al., 1997) and hypothalamic estrogen receptor expressing neurons in rat (Kallo et al., 1992). Synchronized serotonin and dopamine release was reported in the medial and lateral hypothalamus (Fetissov et al., 2000) indicating that Journal of Chemical Neuroanatomy 39 (2010) 235–241 ARTICLE INFO Article history: Received 9 October 2009 Received in revised form 9 January 2010 Accepted 9 January 2010 Available online 18 January 2010 Keywords: Immunohistochemistry Circadian rhythm Mood Neuroendocrine functions Sleep Feeding ABSTRACT Disorders of serotonergic neurotransmission are involved in disturbances of numerous hypothalamic functions including circadian rhythm, mood, neuroendocrine functions, sleep and feeding. Among the serotonin receptors currently recognized, 5-HT 1A receptors have received considerable attention due to their importance in the etiology of mood disorders. While previous studies have shown the presence of 5-HT 1A receptors in several regions of the rat brain, there is no detailed map of the cellular distribution of 5-HT 1A receptors in the rat diencephalon. In order to characterize the distribution and morphology of the neurons containing 5-HT 1A receptors in the diencephalon and the adjacent telencephalic areas, single label immunohistochemistry was utilized. Large, multipolar, 5-HT 1A -immunoreactive (IR) neurons were mainly detected in the magnocellular preoptic nucleus and in the nucleus of diagonal band of Broca, while the supraoptic nucleus contained mainly fusiform neurons. Medium-sized 5-HT 1A -IR neurons with triangular or round- shaped somata were widely distributed in the diencephalon, populating the zona incerta, lateral hypothalamic area, anterior hypothalamic nucleus, substantia innominata, dorsomedial and pre- mamillary nuclei, paraventricular nucleus and bed nucleus of stria terminalis. The present study provides schematic mapping of 5-HT 1A -IR neurons in the rat diencephalon. In addition, the morphology of the detected 5-HT 1A -IR neural elements is also described. Since rat is a widely used laboratory animal in pharmacological models of altered serotoninergic neurotransmission, detailed mapping of 5-HT 1A -IR structures is pivotal for the neurochemical characterization of the neurons containing 5-HT 1A receptors. ß 2010 Elsevier B.V. All rights reserved. * Corresponding author at: Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA 16509, United States. Tel.: +1 814 866 8142; fax: +1 814 866 8411. E-mail address: bdudas@lecom.edu (B. Duda ´ s). Contents lists available at ScienceDirect Journal of Chemical Neuroanatomy journal homepage: www.elsevier.com/locate/jchemneu 0891-0618/$ – see front matter ß 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jchemneu.2010.01.003