Peptides (v.21, #11)
Vittorio Erspamer: A true pioneer in the field of bioactive peptides by Tindaro G Renda (1585-1586).
Parallel bioassay of 39 tachykinins on 11 smooth muscle preparations. Structure and receptor selectivity/affinity relationship 1 1 This is the final paper written by Professor Vittorio Erspamer before he died suddenly in October, 1999. His collaborators are proud to present it on his behalf and to honour his memory. by Cinzia Severini; Severo Salvadori; Remo Guerrini; Giuliana Falconieri-Erspamer; Giuseppina Mignogna; Vittorio Erspamer (1587-1595).
Parallel bioassay on smooth muscle preparations demonstrated that: all TKs having a neutral or basic residue at position 7 from the C-terminus show a clear-cut preference for the NK1 TK receptor, reinforced by the presence of the aromatic doublet Phe-Phe or Phe-Tyr (aromatic TKs); all aliphatic TKs (Phe-Ile/Val) having an acidic residue at position 7 show a clear-cut preference for NK2/NK3 receptors, generally without selectivity for a single receptor. However, in aromatic TKs having the same acidic residue, the preference for NK2/NK3 receptors is weakened, with a more or less pronounced co-preference for the NK1 receptor. Amino acid substitutions in the C-terminal tripeptide may influence receptor affinity.
Keywords: Tachykinins; Parallel bioassay; Smooth muscle preparations; Structure/Receptor selectivity relationship;
The psychopharmacology of tachykinin NK-3 receptors in laboratory animals by Maurizio Massi; Izabela Panocka; Giuseppe de Caro (1597-1609).
The present article reviews the studies so far published on the psychopharmacological effects mediated by tachykinin NK-3 receptors in laboratory animals. Central administration of NK-3 receptor agonists has been reported to attenuate alcohol intake in alcohol-preferring rats and to evoke conditioned place preference. These findings suggest that NK-3 receptors may affect reward processes to drugs of abuse. Anxiolytic-like and antidepressant-like effects have been previously reported for NK-1 receptor antagonists, and anxiolytic-like effects for NK-2 receptor antagonists. More recently, it has been shown that NK-3 receptor agonists have anxiolytic-like and antidepressant-like effects in mice and rats, while an NK-3 receptor antagonist was reported to be anxiogenic in mice. These findings indicate that different TK receptor subtypes may be involved in anxiolytic-like and antidepressant-like effects in laboratory animals and raise interest for the possible role of NK-3 receptors in the control of anxiety and depression in man.
Keywords: Tachykinins; NK-3 receptor agonists; NK-3 receptor antagonists; Reward; Drug abuse; Anxiety; Depression;
Effects of supraspinal administration of PG-SPI and PG-KII, two amphibian tachykinin peptides, on nociception in the rat☆,1 1 1 “In memory of the rigorous but free spirit of Vittorio Erspamer, of his researcher’s enthusiasm, of his intellectual vivacity and of his interior serenity which will stay forever with us, his pupils and coworkers.” by Giovanna Improta; Maria Broccardo (1611-1616).
We investigated and compared the effects of two amphibian tachykinins, the NK1 receptor agonist PG-SPI and the NK3 receptor agonist PG-KII, and the mammalian tachykinins substance P, neurokinin A and neurokinin B on the reaction time to a painful radiant heat stimulus (tail-flick test in rats) after intracerebroventricular injection. PG-SPI (1, 10 and 20 μg) and PG-KII (1, 5 and 10 μg) significantly increased the reaction time. Substance P (10 μg) injected intracerebroventricularly induced antinociception, whereas neurokinin A and neurokinin B did not. Like analgesia evoked by exogenous substance P, PG-SPI-evoked analgesia was blocked by pretreatment with naloxone. Naloxone left PG-KII antinociception unchanged, but the NK3 receptor selective antagonist markedly reduced it. These findings suggest NK1 and NK3 tachykinin receptor system involvement in supraspinal analgesia in rats.
Keywords: PG-SPI; PG-KII; Tachykinin antagonists; Naloxone; Analgesia;
Bombesin and the brain-gut axis☆,1 1 1 This review is dedicated to the memory of Dr. Vittorio Erspamer for his outstanding contributions to the field of peptide research. His pioneering work directed much of our subsequent studies on the central mechanisms regulating gastrointestinal function. by Vicente Martinez; Yvette Taché (1617-1625).
Bombesin is the first peptide shown to act in the brain to influence gastric function and the most potent peptide to inhibit acid secretion when injected into the cerebrospinal fluid (CSF) in rats and dogs. Bombesin responsive sites include specific hypothalamic nuclei (paraventricular nucleus, preoptic area and anterior hypothalamus), the dorsal vagal complex as well as spinal sites at T9-T10. The antisecretory effect of central bombesin encompasses a variety of endocrine/paracrine (gastrin, histamine) or neuronal stimulants. Bombesin into the CSF induces an integrated gastric response (increase in bicarbonate, and mucus, inhibition of acid, pepsin, vagally mediated contractions) enhancing the resistance of the mucosa to injury through autonomic pathways. The physiological significance of central action of bombesin on gastric function is still to be unraveled.
Keywords: Amphibian skin peptides; Regulatory Peptides; Gut function; Gastric secretion; Gastric motility; Hypothalamic nuclei; Vagus nerve; Autonomic pathways;
Bombesin-like peptide and receptors in lung injury models: diverse gene expression, similar function☆,☆☆ 1 1 ☆☆ We are deeply grateful to Professor Vittorio Erspamer, whose vision and life’s work paved the way for these studies. by Anne Cullen; Rodica L Emanuel; John S Torday; Nithiananthan Asokananthan; Kristan A Sikorski; Mary E Sunday (1627-1638).
We previously demonstrated that bombesin-like peptide (BLP) mediates lung injury in premature infants with bronchopulmonary dysplasia (BPD). We now investigate gene expression and function of BLP (gastrin-releasing peptide, GRP) and BLP-receptors (GRP-R and BRS-3) in lung from two baboon BPD models. In the “interrupted gestation model,” only GRP mRNA was up-regulated. In the “hyperoxic model,” GRP-R mRNA was up-regulated. In lung explants from O2-treated animals, all BPD animals responded to 1nM bombesin, whereas non-BPD animals did not; the opposite effect was observed with a BLP blocking antibody. Cumulatively, these observations suggest that novel BLPs and/or BLP receptors are likely to be implicated in the pathogenesis of BPD.
Keywords: Gastrin-releasing peptide/bombesin receptor subtype-3; Bronchopulmonary dysplasia; Premature birth; Hyperoxia; Dexamethasone; Corticotropin-releasing hormone; Neuromedin B; Baboon model;
Pharmacology of Amphibian Opiate Peptides 1 1 This article is dedicated to the memory of professor Vittorio Erspamer whose superb intuition of biological phenomena enriched our knowledge of new unimagined agents and actions. by Lucia Negri; Pietro Melchiorri; Roberta Lattanzi (1639-1647).
In 1980 the skin of certain frogs belonging to the genus Phyllomedusinae was found to contain two new peptides that proved to be selective μ-opioid agonists, and named dermorphins. Since 1987 deltorphins, a family of highly selective δ-opioid peptides were identified either by cloning of the cDNA from frog skins or isolation of the peptides. The distinctive feature of opioid peptides is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe. The discovery of the amphibian opiate peptides, provided new insights into the functional role of the μ- and δ-opiate systems. It also provided models for novel analgesics with enhanced therapeutic benefits and reduced toxicity.
Keywords: Opiate receptors; Peptides; Antinociception; Respiratory depression;
Production and immunohistochemical application of antiserum against Tyr-D-Ala-Phe, a N-terminal tripeptide common to dermorphin/deltorphin family☆,1 1 1 With this article the authors would like to celebrate the memory of Vittorio Erspamer who during the last decade of his life honored them with his warm friendship and wise scientific collaboration. Also the preparation of the antibody here reported was made according to his precise suggestions. by Ikuo Tooyama; Hiromichi Abe; Tindaro G Renda; Hiroshi Kimura (1649-1655).
Tyr-D-Ala-Phe is a N-terminal sequence commonly found in a peptide family including dermorphin and deltorphin. The tripeptide was synthesized and conjugated with poly L-lysine. Nuclear magnetic resonance (NMR) indicated that approximately 38 molecules of the tripeptide were bound to each molecule of poly L-lysine. The conjugate was used to immunize rabbits, and high titer antisera were obtained. An IgG fraction was purified by protein G affinity chromatography. A specific antibody to the tripeptide was then obtained by affinity chromatography using formylcellulofine conjugated with Tyr-D-Ala-Phe. On immunospot assay, the best IgG antibody was capable of detecting 125 ng of Tyr-D-Ala-Phe but failed to react even with 2.0 μg of Tyr-L-Ala-Phe or poly L-lysine. Our immunohistochemical examination selectively localized the secretory glands of frog skin.
Keywords: Amphibian skin peptides; Opioid peptides; Frog skin; NMR analysis; Immunohistochemistry;
Production of monoclonal antibody to deltorphin-I and its immunocytochemical application to adult rat brain and cultured rat brain neurons☆,1 1 1 In memory of Prof. Vittorio Erspamer who during the past ten years continuously encouraged us to do our best to find the mammalian counterpart of deltorphins. by Shun Yu; Tong Zhao; Ming Fan; Ikuo Tooyama; Hiroshi Kimura; Tindaro G Renda (1657-1662).
A monoclonal anti-deltorphin-I antibody specifically recognizing its NH2-terminal region was produced. In the adult rat brain sections, it recognized immunoreactive nerve fibers mainly in the bed nucleus of stria terminalis, central nucleus of amygdala, lateral hypothalamus, hippocampus, substantia nigra, periaqueductal gray and locus ceruleus. Occasionally, positive somata were localized in the bed nucleus of stria terminalis, central nucleus of amygdala, supraoptic and periventricular nuclei. In primarily cultured neurons from various brain regions of new-born rats, the antibody immunostained strongly neuronal somata and processes. The abundant DADTI-immunoreactive substance in the cultured neurons promises to provide an alternative pathway to search for the counterpart of deltorphins in mammals.
Keywords: Opiates; Amphibian skin peptides; Cell culture; Immunocytochemistry; Monoclonal Antibody;
Opioid pseudopeptides containing heteroaromatic or heteroaliphatic nuclei 1 1 This article is dedicated in tribute to the memory of Vittorio Erspamer whose pioneering spirit ushered in the discovery of new, unimagined substances lives ever on. Silence reigns in halls of science as the footfalls of a giant among humankind will no longer awaken our imaginations to the wonders that Nature holds hidden from view. Who will now step forth to carry the light of inquiry and dare to seek the unknown? by Gianfranco Balboni; Severo Salvadori; Remo Guerrini; Clementina Bianchi; Vincenzo Santagada; Giuseppe Calliendo; Sharon D. Bryant; Lawrence H. Lazarus (1663-1671).
In lieu of H-Dmt-Tic-OH, H-Dmt-analogues included 2-amino-3(1H-benzoimidazol-2-yl)-propionic acid, N(Bzl)Gly, l-octahydroindole-2-carboxylic acid, [3S-(3α,4aβ,8aβ)]-decahydro-3-isoquinoline carboxylic acid, benzimidazole-, pyridoindole- or spiroinden-derivatives, or C-terminally modified. l- or d-Ala, Sar, or Pro were spacers between aromatic nuclei. Only H-Dmt-(Xaa-)-pyridoindole exhibited high affinities with δ and μ antagonism. The peptides competed equally against [3H]DPDPE (δ agonist) or [3H]N,N(CH3)2-Dmt-Tic-OH (δ antagonist) signaling a single δ binding site. The data confirm the importance of Tic for δ affinity and antagonism, while heterocyclic or heteroaliphatic nuclei, or spacer exert effects on μ- and δ-receptor properties.
Keywords: Agonism; Antagonism; Dmt; Dmt-Tic pharmacophore; Opioid peptides; Peptide synthesis; Pharmacological bioassays; Receptor affinities;
Structure-function relationships in bombinins H, antimicrobial peptides from Bombina skin secretions☆ 1 1 ☆ This paper is dedicated to the memory of our much-missed Professor Vittorio Erspamer, Magister of science and life, who paved the way for great discoveries in molecular pharmacology. by M.Luisa Mangoni; Nicoletta Grovale; Alessandra Giorgi; Giuseppina Mignogna; Maurizio Simmaco; Donatella Barra (1673-1679).
Skin secretions of amphibia of the Bombina genus contain two families of antimicrobial peptides, the bombinins (bombinin-like peptides) and the bombinins H (H for hydrophobic and hemolytic). The latter family includes a number of peptides containing a D-amino acid in the second position, in addition to their corresponding all L-isomers. The antimicrobial activity of three pairs of bombinin H isomers, H2/H4, H6/H7 and GH-1D/GH-1L, has been investigated. The first two pairs of peptides were actually isolated from the secretion, whereas the third was synthesized according to the sequence deduced from a gene coding for a bombinin-like peptide in Bombina orientalis.
Keywords: Antimicrobial peptides; Bombinin H; D-amino acid; Amphibia; Bombina genus;
Sequence of a gene from Bombina orientalis coding for the antimicrobial peptide BLP-7 by Rossella Miele; Marina Borro; Daniela Fiocco; Donatella Barra; Maurizio Simmaco (1681-1686).
The structure of a gene coding for bombinin-like peptides (BLP) in Bombina orientalis was determined. It comprises two exons separated by a 1337 bp intron. Exon 1 codes for the signal peptide, while exon 2 contains the genetic information for BLP-7 and a bombinin H-type peptide (GH-2). The promoter region contains putative recognition sites for nuclear factors, such as NF-IL6 and NF-κB. The analysis of the structure of this gene, compared with that of the previously reported BLP-3 gene sequence, suggests the occurrence of a gene duplication event, rather than an alternative splicing mechanism, which leads to the generation of both inter- and intra-families variability in this class of cytolytic peptides. Furthermore, walking chromosome analysis indicates that this gene family is not densely clustered.
Keywords: Bombinin (BLP); Bombinin H; Antimicrobial peptide gene; Amphibia; Bombina orientalis;
Expression and Motor Effects of Secretin in Small and Large Intestine of the Rat☆,1 1 1 Dedicated to the memory of Professor Vittorio Erspamer, an eminent scientist and one of the true founders of the field of regulatory peptide research, a field attracting a steadily increasing number of scientists and influencing many branches of biomedical research. by Amelie Andersson; Frank Sundler; Eva Ekblad (1687-1694).
Immunocytochemistry and in situ hybridization revealed abundant secretin expressing cells on duodenal villi with a gradual decrease throughout the small intestines of the rat. They were absent in pancreas, stomach and colon. Secretin caused relaxation of rat intestinal longitudinal muscle in vitro. Studies on colon revealed that the secretin-evoked response was unaffected by apamin, tetrodotoxin, L-NAME, VIP or PACAP pretreatment; secretin itself caused desensitization. Addition of VIP or PACAP when the secretin-evoked relaxation was maximal evoked a further relaxation suggesting the presence of distinct receptors.Secretin causes relaxation via activation of secretin receptors located on the smooth muscle and not via any of the related VIP/PACAP receptors.
Keywords: VIP; PACAP; Secretin receptor; Intestinal relaxation; Gut hormones;
Expression of mammalian RF-amide peptides neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and the PrRP receptor in the peripheral tissues of the rat☆,☆☆ 1 1 ☆☆ Dedicated to the memory of Professor V. Erspamer, who was always willing to help others and whose work on novel peptides was a major source of inspiration. by Maija-Liisa Nieminen; Annika Brandt; Pirjo Pietilä; Pertti Panula (1695-1701).
The mRNA expression of neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and the UHR-1/GPR10 receptor were examined using in situ hybridization in rat peripheral tissues. In the hypophysis, modest expression of PrRP and receptor mRNA were seen in the anterior lobe. The trigeminal ganglion was devoid of expression signals. PrRP and UHR-1/GPR10 receptor mRNA:s were found in the adrenal medulla and PrRP mRNA was found in the pancreas. NPFF mRNA was detected in the spleen. In the testis and epididymis, PrRP and UHR-1/GPR10 receptor mRNA:s were detected. The results suggest a limited expression of mammalian RF-amide peptides in the peripheral organs.
Keywords: Antiopioid peptide; Morphine-modulating peptide; Pituitary gland; Prolactin; Adrenal medulla;
Ontogeny of PACAP immunoreactivity in extrinsic and intrinsic innervation of chicken gut☆,1 1 1 To honor the memory of Professor Erspamer who represented for us a model to follow in our research and lifestyle. by Ebe Parisi Salvi; Rosa Vaccaro; Tindaro G Renda (1703-1709).
An immunohistochemical study was conducted on the ontogeny of pituitary adenylate cyclase-activating polypeptide-27 (PACAP) immunoreactive elements within the extrinsic and intrinsic nerve supply of the chicken embryo gut. The first PACAP-immunoreactivity was detected in the extrinsic nerve supply at E 4 within the pharyngeal region and the primary sympathetic chain. At E 5.5 it appeared in the vagus nerve, the spinal cord, the secondary sympathetic chain, some perivascular plexuses and the Remak ganglion. In the intrinsic nerve supply, the first PACAP-immunoreactive elements were shown at E 4.5-E 5 in the mesenchymal bud of the proventriculus/gizzard. Then they gradually appeared also cranially and caudally both in myenteric and submucous plexuses.
Keywords: VIP; Autonomic Nerve system; Chick embryo; immunohistochemistry; Development;
Galanin coexists with pituitary hormones in the fetal rat☆,★ 1 1 ★ I particularly remind Prof. Erspamer and his humanity. I met him before my first talk to an international conference. I was nervous, but I felt much better after Erspamer’s warm encouragement. by Vincenzo Cimini (1711-1716).
Immunocytochemical analysis of endocrine cells of the developing rat pituitary has shown clearly that, starting from E16, the galanin-immunoreactive cells are heterogeneous, the neuropeptide being present in cells containing the majority of pituitary hormones. A proportion of galanin-containing corticotropes, starting from about 17% at E16 reached about 29% at E21, while the galanin-containing lactotrope increase in the same period was from about 13% to 34%. Galanin-containing thyrotropes ranged from about 11% at E16 to about 13% at E21, while the proportion of galanin-containing luteotropes increased consistently from about 17% at E19 to about 27% at E21. Only the trend of galanin-containing somatotropes was inverted, falling from about 26% to 13%. We conclude that the multiple coexistence of galanin with most of the pituitary hormones during fetal development is a further example of plasticity of endocrine pituitary cells, and that galanin may have a role in cytodifferentiation.
Keywords: Ontogeny; Pituitary gland; Multiple coexistence; Immunocytochemistry;
Aminoacyl-histidine dipeptides in the glial cells of the adult rabbit forebrain☆,1 1 1 In memory of Vittorio Erspamer who gave me through the years invaluable expertise on amphibian skin peptides and carnosine, but far more an outstanding example in life and science. (A.F.). by Paolo Peretto; Federico Luzzati; Luca Bonfanti; Silvia De Marchis; Aldo Fasolo (1717-1724).
The mammalian nervous system contains high amounts of the aminoacyl-histidine dipeptides carnosine and homocarnosine. In the brain, they prevalently occur mainly in glial and ependymal cells, their role(s) still remaining obscure. In vitro studies indicate that these molecules exert diverse protective effects, and in vivo they are frequently associated with extracellular fluid compartments. Recently, carnosine-like immunoreactivity has been found in the subependymal layer (SEL) of adult rodents, a region endowed with persistent cell proliferation and migration. Unlike rodents, the SEL of the rabbit has a persistent olfactory ventricle. We show here that the morphologic organization of the SEL is different in these species, with particular reference to the glial/non glial cell compartments. The distribution of carnosine-like immunoreactivity in the rabbit displays some differences only within the SEL, which could be linked to its arrangement and compartmentalization.
Keywords: Carnosine; Subependymal layer; Neurogenesis; Immunohistochemistry;
Effects of centrally administered galanin (1–16) on galanin expression in the rat hypothalamus1 1 1 This work is dedicated to V. Erspamer’s memory. by Marc Landry; Danièle Roche; Evelyne Vila-Porcile; André Calas (1725-1733).
In the rat hypothalamic magnocellular neurons, galanin coexists with vasopressin and might be involved in hydro-osmotic regulation. In the present study, we investigated the ability of galanin to also regulate the osmotically stimulated expression of galanin itself in hypothalamic magnocellular neurons. Ten minutes after galanin injection, galanin mRNA rate decreased in salt-loaded rats whereas the level of galanin immunoreactivity increased. Both effects were suppressed by the injection of a galanin antagonist together with galanin. Moreover, electron microscope studies demonstrated synaptic contacts between galanin-containing fibers and magnocellular neurons. Galanin may exert inhibitory roles in the regulation of magnocellular neurons. However, galanin and vasopressin expression displayed differences upon galanin injection. Possible mechanisms underlying these discrepancies are further discussed.
Keywords: neuropeptides; galanin; hypothalamus; osmotic regulation; immunohistochemistry; in situ hybridization; quantification;
Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study☆ by Gabriella Moldrich; Tibor Wenger (1735-1742).
The presence of central cannabinoid receptor (CB1), involving the N-terminal 14 amino acid peptide, was demonstrated in the rat brain by immunohistochemistry. Intensely stained neurons were observed in the principal neurons of the hippocampus, striatum, substantia nigra, cerebellar cortex, including the Purkinje cells. Moderate CB1-IR cell bodies and fibers were present in the olfactory bulb, cingulate, entorhinal and piriform cortical areas, amygdala and nucleus accumbens. The perivascular glial fibers have shown moderate to high density CB1-IR in olfactoric and limbic structures. Low density was detected in the thalamus and hypothalamus and area postrema. The CB1 receptor was widely distributed in the forebrain and sparsely in the hindbrain.These new data support the view that the endogenous cannabinoids play an important role in different neuronal functions as neuromodulators or neurotransmitters.
Keywords: Endogenous cannabinoid; Olfactory system; Limbic system; Cerebellum;
Immunohistochemical localization of amylin in rat brainstem☆,☆☆ 1 1 ☆☆ To honor the memory of Professor Vittorio Erspamer, a true scientist and a very wise man, who during the last twenty-five years honored us with his sincere friendship. by Loredana D’Este; Arianna Casini; Sunil J Wimalawansa; Tindaro G Renda (1743-1749).
Immunohistochemical studies were conducted on rat brainstem using a specific polyclonal antiserum against the COOH-terminal (25–37) of human amylin. Amylin-immunoreactive cell bodies were observed in the vestibular, cochlear, trapezoid, and inner cerebellar nuclei and in the mesencephalic nucleus of trigeminal nerve. Positive cell bodies were also found in lateral, gigantocellular and magnocellular reticular nuclei. Numerous amylin-immunoreactive nerve fibers were shown in the trigeminal spinal tract, in the solitary area and in the area postrema. Amylin-immunoreactive cell bodies were often surrounded by a network of tyrosine hydroxylase-immunoreactive nerve fibers. These results provide morphologic evidence that amylin may play a role in some discrete sensory functions.
Keywords: Islet amyloid polypeptide; Neuropeptides; Regulatory peptides; CGRP; Tyrosine hydroxylase; Reticular formation; Locus coeruleus; Vestibular pathways; Cochlear pathways; Trigeminal nuclei; Vagus nerve; Area postrema;
Effects of intra-VTA injection of neurotensin on local cerebral glucose utilization in freely moving rats☆,☆☆ 1 1 ☆☆ We would like to dedicate this work to Vittorio Erspamer. by Francesco E Pontieri; Maurizia Rasura; Alessandra Scontrini; Francesca R Buttarelli (1751-1753).
The [14C]2-deoxyglucose method was applied to measure the effects of the injection of neurotensin (7 μg) in the ventral tegmental area on local cerebral glucose utilization in the rat. Injection of neurotensin produced significant increases of glucose utilization in the shell of the nucleus accumbens and in the olfactory tubercle. These results indicate that stimulation of neurotensin receptors in the ventral tegmental area produces functional changes that are confined to the regions receiving mesolimbic projections within the rostral extended amygdaloid complex. These findings extend our understanding on the effects of neurotensin in the limbic system, with particular regard to reward pathways.
Keywords: Neuropeptides; Deoxyglucose; Cerebral metabolism; Nucleus accumbens; Shell; Dopaminergic system; Mesolimbic pathways;
Isolation-rearing of rats produces deficits as adults in the serotonergic innervation of hippocampus by P Whitaker-Azmitia; F Zhou; J Hobin; A Borella (1755-1759).
Isolation-rearing of rats causes a variety of behavioral changes, including anxiety, learning deficits and sensory changes related to schizophrenia. Similar changes are seen following loss of serotonin during development. Thus, the effects of isolation-rearing on behavior may be due to changes in serotonin.Sprague-Dawley rats were raised in groups of four (social animals) or in isolation, from postnatal day 22 until postnatal day 64. The hippocampi were examined immunochemically for changes in serotonin. Our findings show that serotonin terminals are lost throughout the CA regions of hippocampus, where there is also an associated loss of dendrites, but not in the molecular layer of the dentate gyrus. Thus, some of the brain and behavioral changes seen in isolation-reared animals could be due to loss of serotonin.
Keywords: MAP-2; Hippocampus; Schizophrenia;