Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice

Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotio...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Datum:2011
Hauptverfasser: Amikishieva, A.V., Ilnitskaya, S.I., Nikolin, V.P., Popova, N.A.
Format: Artikel
Sprache:English
Veröffentlicht: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2011
Schriftenreihe:Experimental Oncology
Schlagworte:
Online Zugang:https://nasplib.isofts.kiev.ua/handle/123456789/138660
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Zitieren:Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice / A.V. Amikishieva, S.I. Ilnitskaya, V.P. Nikolin, N.A. Popova // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 126-129. — Бібліогр.: 25 назв. — англ.

Institution

Digital Library of Periodicals of National Academy of Sciences of Ukraine
id nasplib_isofts_kiev_ua-123456789-138660
record_format dspace
spelling nasplib_isofts_kiev_ua-123456789-1386602025-02-23T18:58:23Z Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice Amikishieva, A.V. Ilnitskaya, S.I. Nikolin, V.P. Popova, N.A. Original contributions Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotional state on tumor progression. Methods: Anxiety-like psychoemotional state of the animals was produced using chronic social conflict model. Used behavioral tests were elevated plus-maze, social interaction test and open field test. Tumor cells were administrated on background of double or sixfold SSR149415 injections and the number of metastases in the lung were calculated 17 days later. Results: SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze and social interaction tests and did not affect locomotor activity in the open field test. Double and sixfold administration of the compound to such mice before and after inoculation of the tumor cells produced no effect on the metastasis rate. Conclusion: vasopressin V1b receptor is involved in the mediation of anxious behavior of animals but is not involved in the mechanism underlying the influence of negative psychoemotional state on Lewis lung carcinoma metastasis. The authors are grateful to Dr. Claudine SerradeilLe Gal (Sanofi Eventis Recherche & Developpement, France) for kind provision of V1b receptor antagonist. 2011 Article Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice / A.V. Amikishieva, S.I. Ilnitskaya, V.P. Nikolin, N.A. Popova // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 126-129. — Бібліогр.: 25 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138660 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Amikishieva, A.V.
Ilnitskaya, S.I.
Nikolin, V.P.
Popova, N.A.
Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
Experimental Oncology
description Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotional state on tumor progression. Methods: Anxiety-like psychoemotional state of the animals was produced using chronic social conflict model. Used behavioral tests were elevated plus-maze, social interaction test and open field test. Tumor cells were administrated on background of double or sixfold SSR149415 injections and the number of metastases in the lung were calculated 17 days later. Results: SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze and social interaction tests and did not affect locomotor activity in the open field test. Double and sixfold administration of the compound to such mice before and after inoculation of the tumor cells produced no effect on the metastasis rate. Conclusion: vasopressin V1b receptor is involved in the mediation of anxious behavior of animals but is not involved in the mechanism underlying the influence of negative psychoemotional state on Lewis lung carcinoma metastasis.
format Article
author Amikishieva, A.V.
Ilnitskaya, S.I.
Nikolin, V.P.
Popova, N.A.
author_facet Amikishieva, A.V.
Ilnitskaya, S.I.
Nikolin, V.P.
Popova, N.A.
author_sort Amikishieva, A.V.
title Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
title_short Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
title_full Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
title_fullStr Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
title_full_unstemmed Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
title_sort effect of vasopressin v1b receptor antagonist, ssr149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2011
topic_facet Original contributions
url https://nasplib.isofts.kiev.ua/handle/123456789/138660
citation_txt Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice / A.V. Amikishieva, S.I. Ilnitskaya, V.P. Nikolin, N.A. Popova // Experimental Oncology. — 2011. — Т. 33, № 3. — С. 126-129. — Бібліогр.: 25 назв. — англ.
series Experimental Oncology
work_keys_str_mv AT amikishievaav effectofvasopressinv1breceptorantagonistssr149415onanxietylikebehaviorandlewislungcarcinomametastasisinmice
AT ilnitskayasi effectofvasopressinv1breceptorantagonistssr149415onanxietylikebehaviorandlewislungcarcinomametastasisinmice
AT nikolinvp effectofvasopressinv1breceptorantagonistssr149415onanxietylikebehaviorandlewislungcarcinomametastasisinmice
AT popovana effectofvasopressinv1breceptorantagonistssr149415onanxietylikebehaviorandlewislungcarcinomametastasisinmice
first_indexed 2025-11-24T12:45:37Z
last_indexed 2025-11-24T12:45:37Z
_version_ 1849675835251884032
fulltext 126 Experimental Oncology 33, 126–129, 2011 (September) EffEct of VasoprEssin V1b rEcEptor antagonist, ssr149415, on anxiEty-LikE bEhaVior and LEwis Lung carcinoma mEtastasis in micE A.V. Amikishieva*, S.I. Ilnitskaya, V.P. Nikolin, N.A. Popova Institute of Cytology and Genetics of Siberian Department of Russian Academy of Sciences, Novosibirsk, Russian Federation 630090 Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carci- noma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotional state on tumor progression. Methods: Anxiety-like psychoemotional state of the animals was produced using chronic social conflict model. Used behavioral tests were elevated plus-maze, social interaction test and open field test. Tumor cells were administrated on background of double or sixfold SSR149415 injections and the number of me- tastases in the lung were calculated 17 days later. Results: SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze and social interaction tests and did not affect locomotor activity in the open field test. Double and sixfold administration of the compound to such mice before and after inoculation of the tumor cells produced no effect on the metastasis rate. Conclusion: vasopressin V1b receptor is involved in the mediation of anxious behavior of animals but is not involved in the mechanism underlying the influence of negative psychoemotional state on Lewis lung carcinoma metastasis. Key Words: anxiety, Lewis lung carcinoma, metastasis, vasopressin receptor, SSR149415 The effect of psychoemotional state on tumor pro- gression is an established phenomenon although its underlying mechanisms remain elusive. Three decades ago it was demonstrated that rearing of animals in over- crowded conditions and subsequent activation of the stress system of organism can significantly change the incidence of tumors and the number of tumor metastatic nodules [22]. The study of two types of transplantable tumors carried out in mice showed that animals with anxiety-like behavior induced by rearing in stressful conditions have twice as much of experimental me- tastases as intact mice [10, 16], while anxiolytic drug diazepam reduces the number of metastases [9]. Hypothalamic hormone vasopressin potentiating the action of corticoliberin can increase the secretion of the adrenocorticotropic hormone and subserves significantly to the formation of negative stress- induced psychoemotional states [13, 23]. Distribution of vasopressinergic fibers and receptors in the limbic structures of the brain suggests the involvement of this neuropeptide in emotional responses to stress [11]. The animals with depression semiotics and patients with major depression were shown to have an in- creased plasmatic level of vasopressin. In both cases administration of antidepressants normalizes the hormone level [4, 12]. Rats selected for high anxiety behavior exhibit innate elevated expression of vaso- pressin mRNA and hypothalamic receptor binding [18]. Exogenous intraventricularly administered vasopres- sin produces anxiogenic effect while its antagonists alleviate the symptoms of anxiety [2, 7]. Clinically ef- fective anxiolytic drugs reduce the expression of the vasopressin precursor gene [23]. In the experiments with Lewis lung carcinoma (LLC) metastasis, administration of vasopressin was shown to increase the number of metastatic nodules in the lungs of mice [1], similarly as it occurs in animals with an impaired psychoemotional state. Still it is so far not clearly how the mechanisms of vasopressin action on metastasis and psychoemotional state interrelate. Physiological action of vasopressin is known to be mediated by receptors of three types: V1a, V1b, and V2. The receptors of the former two types are widespread in the CNS structures [8, 20] and are in- volved in anxious behavior [5]. Receptors of V1a type are also present on unstriped muscles of the brain vessels and V1b receptors — on corticotroph pituitary cells to implement the effect of vasopressin on the stress axis of organism [21]. Receptors of both types are sensitive to emotional stress. Anxiety-like behav- ior in animals correlates with enhanced V1-receptor binding in the CNS [12]. Addition of antisense mRNA of V1a receptor to mice results in a pronounced allevia- tion of anxiety-like behavior and impairment of social recognition. Chronic immobilization stress increases V1a mRNA level in rat brain [17]. Recently synthesized specific vasopressin V1b- receptor antagonist, SSR 149415 [7] provides the opportunity for distinguishing the contribution of re- ceptors of this type to increasing of tumor metastasis in animals with pronounced anxiety-like behavior, which has become the purpose of this study. matEriaLs and mEthods Animals. Male C56B1/6J strain mice, weigh- ing 25–28 g, housed in standard conditions of the vivarium of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences Received: May 23, 2011. *Correspondence: E-mail - amik@bionet.nsc.ru Fax - 7 383 333 12 78 Abbreviations used: CNS – central nervous system; EPM - el- evated plus-maze; LLC – Lewis lung carcinoma. Exp Oncol 2011 33, 3, 126–129 Experimental Oncology 33, 126–129, 2011 (September) 127 were used. All experimental procedures with animals were carried out in accordance with the international rules established by the European Community Council Directive (86/609/EEC). Anxious pattern of mice behavior was produced using a 10-day chronic social conflict model [15]. Behavior Evaluation Methods The elevated plus-maze (EPM). This method is used to measure anxiety-like behavior of the mice placed in unfamiliar environment [24]. The four-minute experimental sessions were recorded with video camera. The conventional behavioral measures were recorded with the use of the “Mouse” software pack- age (Institute of Cytology and Genetics, SB RAS). The most significant anxiety-related measures included time spent in the central area of the maze, time in the closed arms and time in the open arms and area (sum of central area and open arms times), and latent period of closed-arm entries. Exploratory behavior measures were the number of dipping postures with head below the level of the maze and stretching postures. The “Partition” social interaction test. This test is used to obtain quantitative measures of sociability (communicativeness) of the animals relative to the level of anxiety [6]. The behavior of the mice in anxiety- like state was assessed in response to a known aggres- sive male and a strange male placed by turns in the neighboring compartment of the home cage across a perforated transparent partition. During the 6-minute test periods (3+3), the number of approaches and time at the partition were recorded for the test male and the derived measure — average time at the partition per approach — was calculated as an indirect measure of communicative motivation of the mice. Open field test. This test is used to evaluate lo- comotor and exploratory activities. Three-minute test sessions were recorded with video camera. The be- havior of the mice was recorded and calculations were made to find the distance, average speed, immobility time, number of upright postures and explorations of the setting holes as well as the time in the central and peripheral zones of the setting. Oncological Experiments. Lewis lung carcinoma cells were inoculated into the tail vein (0.5 ml of sus- pension, 170 thousands cells/mouse). Seventeen days later the mice were decapitated; the lungs were fixed in 10% formalin solution. The number of metastatic nodules was calculated under a microscope with 8-fold magnification. Two experiments were performed: double administration of SSR149415 — a day be- fore and on the day of the tumor cell inoculation; sixfold administration of SSR149415 — once a day during 6 days. Tumor cells were inoculated on the fourth day of SSR149415 injections. Pharmacology. Vasopressin V1b receptor an- tagonist, SSR149415, (10 mg/kg, suspended in 0.6% methylcellulose and 0.5% Tween solution) was admin- istrated once 1 hour before the behavioral tests. Also, in the day of tumor cell inoculation, the compound was administrated 1 hour before LLC cell injection too. Since the drug is known to be equally active at intraperitoneal and oral administration [7], both methods were used in our experiments. The vehicle in equal volumes was administered by the same methods to control mice. Statistical Processing. The results were analyzed with the use of Student’s t-criterion using STATISTIKA 6.0 software package. Each experimental group con- sisted of 11–15 animals. rEsuLts Behavioral tests Elevated plus-maze. Intraperitoneal adminis- tration of SSR149415 significantly reduced the level of anxiety-like behavior in animals (Table 1). The mice spent almost twice as less time in the EPM closed arms and thrice as much time in the open areas as compared to control. The latent period for entries into the closed arms also grew significantly. The time of staying in the center of the maze increased 2.5 times versus the con- trol, which could be interpreted as a reduced speed of “decision making” on the backdrop of the drug action. Exploratory activity measures — dipping postures with heads below the maze and stretching postures showed no reliable difference from the control values mainly due to a considerable scattering of data. Table 1. Effect of vasopressin receptor antagonist, SSR149415, on the be- havior of male mice with anxiety-like behavior in elevated plus-maze test Anxious animals + vehicle (15) Anxious animals + SSR149415 (13) Time in closed arms, sec 195.53 ± 13.96 109.92 ± 25.11 ** Latent period of closed arm entry, sec 19.20 ± 7.31 78.46 ± 25.50 * Time in open arms, sec 5.60 ± 2.73 29.69 ± 18.06 Time in the center of the maze, sec 38.00 ± 13.34 97.77 ± 22.90 * Time in open areas, sec 43.60 ± 13.76 127.46 ± 25.85 ** Number of dipping postures 2.87 ± 0.82 5.46 ±1.14 Number of stretching postures 0.73 ± 0.41 2.69 ± 1.00 Note. *р<0.05; **p<0.01 compared to animals with anxiety, administra- tion of the vehicle. “Partition” social interaction test. Oral adminis- tration of SSR149415 produced no effect on the main measure of communicativeness — time spent by the mice at the partition exploring the smell of a male placed in the neighboring compartment (Table 2). Nonetheless, the drug administration to male mice with anxiety-like symptoms in the situation with unfa- miliar male behind the partition doubled the derived measure — the time at the partition per approach — as compared to control mice suggesting an enhance- ment in mice motivation for communication with a conspecific and reduction of anxiety-like behavior following the administration of SSR149415. Table 2. Effect of vasopressin receptor antagonist, SSR149415, on the be- havior of male mice with anxiety-like behavior in the social interaction test Anxious animals + vehicle (15) Anxious animals + SSR149415 (11) Familiar male: Number of interactions (N) Time of interactions (T), sec Average interaction time (T/N), sec 4.23 ± 0.43 3.90 ± 0.85 41.31 ± 7.73 38.70 ± 6.12 9.69 ± 1.59 12.44 ±2.30 Unfamiliar male: Number of interactions 4.13 ± 0.75 3.09 ± 0.77 Time of interactions, sec 67.47 ± 12.17 69.73 ± 10.79 Average interaction time, sec 17.37 ± 1.72 34.76 ± 8.15 * Note. *р<0.05; **p<0.01 compared to animals with anxiety-like behavior receiving the vehicle. 128 Experimental Oncology 33, 126–129, 2011 (September) Open field test. Oral administration of SSR149415 did not affect locomotor or exploratory activity of animals with anxiety-like behavior in the test (Table 3). Table 3. Effect of vasopressin receptor antagonist, SSR149415, on the behavior of male mice with anxiety-like behavior in open field test Anxious animals + vehicle (15) Anxious animals + SSR149415 (11) Passage distance, cm 290 ± 37 308 ± 42 Immobility time, sec 49.3 ±10.4 62.4 ± 9.6 Speed (distance/time in motion, cm/sec) 2.2 ± 0.2 2.5 ±0.3 Time in the central area, sec 50.2 ± 10.2 36.0 ± 7.4 Time in peripheral area, sec 130.8 ± 10.1 142.2 ±7.6 Number of holes explored 6.4 ± 1.1 5.3 ± 1.1 Number of vertical postures 3.1 ± 0.7 2.7 ± 0.7 metastasis As a rule, the number of LLC metastatic nodules in the lungs positively correlates with the level of anxiety in animals. In our experiments this correlation was reli- ably reproduced in the second experiment (Table 4). Table 4. Effect of vasopressin receptor antagonist, SSR149415, on me- tastasis of Lewis lung carcinoma in the lungs of male mice with anxiety- like behavior Number of meta- static nodules Experiment 1: Intact animals + vehicle 9.9 ± 1.7 (14) Animals with anxiety-like behavior + vehicle 12.8 ± 1.34 (15) Animals with anxiety-like behavior + SSR149415 14.54 ± 1.93 (13) Experiment 2: Intact animals + vehicle 8.2 ± 1.3 (11) Animals with anxiety-like behavior + vehicle 14.7 ± 2.2 (15) * Animals with anxiety-like behavior + SSR149415 15.0 ± 2.2 (14) Note *р<0.05 as compared with intact animals receiving the vehicle. In the first experiment, after double intraperitoneal administration of SSR149415 to mice with anxiety-like behavior the number of metastatic nodules did not change as compared with administration of vehicle to control group. In the second experiment, after six oral administra- tions of SSR149415 the number of metastatic nodules did not differ from control values. discussion Possible influence of emotional state of an indi- vidual on the course of tumor progression has been of interest exclusively for practicing psychologists [3, 25]. In the literature under discussion is whether and to what degree psychotherapy can influence the treatment of patients with tumors. The opinions on this topic seem to be equally divided. We failed to find any biochemical studies aiming to elicit the correlation between psychoemotional state of patients (includ- ing the activity of hypothalamus-pituitary-andrenal axis and vasopressinergic systems) and the efficacy of anticancer therapy. The studies of the last decade demonstrated that vasopressin is a principal regulator of emotional be- havior. Studies in humans support the co-activation of the central vasopressinergic system at anxiety and depression disorders [23] while clinically effec- tive anxiolytic drugs and antidepressants reduce the expression of the vasopressin gene in the CNS [4]. It is vasopressin that provokes hyperactivation of the hypothalamus-pituitary-adrenal axis under chronic emotional stress by acting on pituitary corticotrophs through V1b receptors [14]. The leading role of vasopressin in behavioral phenomena of anxiety and depression and in stress- induced diseases was also demonstrated on animal models [18]. The Brattleboro rates deficient for vaso- pressin gene demonstrate elements of depression-like behavior [19]. In our experiment with mice a single subcutaneous administration of vasopressin caused behavioral reactivity of animals in the open field test [1]. In our experiments anxiety-like behavior was formed during 10 days by means of daily 10-minute agonistic interactions with a stronger male who was kept during the rest of the day in the neighboring compartment of the cage behind a perforated trans- parent partition. This procedure is sufficient to form a stable anxiety-like state in experimental animals [15]. Administration of V1b receptor antagonist, SSR149415, resulted in a visible reduction of anxiety level in the elevated cross-maze test and an increase of motivation in animals with anxiety-like behavior for social interaction with a strange male in the partition test. Therefore, in our experiments we reproduced the results confirming the anxiolytic effect of the drug [7]. After injection of vasopressin antagonist no changes in locomotor activity were recorded. Tumor cells were inoculated 1–2 days after the last fighting. Administration of SSR149415 was made in the 1st experiment a day before and tumor cell administra- tion day; in the 2nd experiment — 3 days before, during carcinoma cells inoculation day and two next days. The hours and days immediately after inoculation are thought to be a sensitive period for tumor cells dis- semination and future growth of metastatic nodules. During this period, double and sixfold administration of SSR149415 did not change the increased intensity of Lewis lung carcinoma cells metastasis in animals with anxiety-like behavior irrespective of the route of drug administration. These results provide more assurance to claim that the previously found enhanc- ing effect of a single vasopressin administration on the process of malignant metastasis is mediated not by V1b receptors. In other words, the V1b receptors are not involved in tumor cell dissemination and growth and the hormone action is not due to its psychotropic behaviorally inhibiting effect. In this situation V1a receptors preserve their appeal to researchers as possible mediators of vasopressin effect on metastasis. Receptors of this type are located in different regions of the brain and blood vessels and together with V1b receptors are involved in behavioral phenomena [20]. The latter site of action of the vaso- pressinergic hormone can influence dissemination of tumor cells by luminal narrowing of lungs vessels under the effect of vasopressin. acknowLEdgmEnts The authors are grateful to Dr. Claudine Serradeil- Le Gal (Sanofi Eventis Recherche & Developpement, France) for kind provision of V1b receptor antagonist. Experimental Oncology 33, 126–129, 2011 (September) 129 rEfErEncEs 1. Amikishieva AV, Ilnitskaya SI, Popova NA, et al. Vaso- pressin as stimulator of the cancerous growth metastases. Eur J Neuropsychopharmacol 2009; 19: 350. 2. Bhattacharya SK, Bhattacharya A, Chakrabarti A. Anxiogenic activity of intraventricularly administered arginine- vasopressin in the rat. Biogen Amine 1998; 14: 367–85. 3. Bukhtoyarov OV, Arkhangelsky AE. Psychogenic death in oncology: validation, pathogenesis, development patterns and prophylactic potential. Vopr Onkol 2006; 52: 708–15 (In Russian). 4. De Bellis MD, Gold PW, Geracioti TD, et al. Association of fluoxetine treatment with reductions in CSF concentrations of corticotrophin-releasing hormone and arginine vasopressin in patients with major depression. Am J Psychiatry 1993; 150: 656–7. 5. Engin E, Treit D. Dissociation of the anxiolytic-like effects of Avp1a and Avp1b receptor antagonists in the dorsal and ventral hippocampus. Neuropeptides 2008; 42: 411–21. 6. File SE, Seth P. A review of 25 years of the social inter- action test. Eur J Pharmacol 2003; 463: 35–53. 7. Griebel G, Simiand J, Serradeil-Le Gal C, et al. Anx- iolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disor- ders. PNAS 2002; 99: 6370–5. 8. Hernando F, Schoots O, Lolait SJ, et al. Immunihis- tochemical localization of the vasopressin V1b receptor in the rat brain bad pituitary gland: anatomical support for its involvement in the central effects of vasopressin. Endocrinol 2001; 142: 1659–68. 9. Kaledin VI, Ilnitskaya SI, Nikolin VP, et al. Limiting effect of diazepam on Lewis lung carcinoma metastasis in anxious male mice. Exp Oncol 2009; 31: 62–4. 10. Kaledin VI, Tenditnik MV, Nikolin VP, et al. Effect of psychoemotional state on growth and metastasis of Lewis tu- mor in mice. Dokl Akad Nauk 2006; 406: 272–4 (In Russian). 11. Kalsbeek A, Palm IF, Buijs RM. Central vasopressin systems and steroid hormones. Prog Brain Res 2002; 139: 57–73. 12. Keck ME, Welt T, Muller MB, et al. Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model. Neuropsychopharmacol 2003; 28: 235–43. 13. Kovacs KJ. Functional neuroanatomy of the parvo- cellular vasopressinergic system: transcriptional responses to stress and glucocorticoid feedback. Prog Brain Res 1998; 119: 31–43. 14. Kovacs KJ, Foldes A, Sawchenko PE. Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. J Neurosci 2000; 20: 3843–52. 15. Kudryavtseva NN. Experience of defeat decreases the behavioral reactivity to conspecifics in the partition test. Behav Proc 1994; 32: 297–304. 16. Kudryavtseva NN, Tenditnik MV, Nikolin VP, et al. The influence of psychoemotional status on metastasis of Lewis lung carcinoma and hepatocarcinoma-29 in mice of C57Bl/6J and CBA/Lac strains. Exp Oncol 2007; 29: 35–8. 17. Landgraf R, Gerstberger R, Montkowski A, et al. V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 1995; 15: 4250–8. 18. Landgraf R, Wigger A. High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety. Behav Genet 2002; 32: 301–14. 19. Mlynarek M, Zelena D, Bagdy G, et al. Signs of at- tenuated depression-like behavior in vasopressin deficient Brattleboro rats. Horm and Behav 2007; 51: 395–405. 20. Ostrowski NL, Lolait SJ, Young WS. Cellular localiza- tion of vasopressin V1a receptor messenger ribonucleic acid in adult male rat brain, pineal, and brain vasculature. Endocrinol 1994; 135: 1511–28. 21. Rene P, de Keyzer Y. The vasopressin receptor of cor- ticotroph pituitary cells. Prog Brain Res 2002; 139: 345–57. 22. Riley V. Psychoneuroendocrine influence on im- munocmpetence and neoplasia. Science 1981; 212: 1100–9. 23. Ring RH. The central vasopressinergic system: examin- ing the opportunities for psychiatric drug development. Curr Pharm Des 2005; 11: 205–25. 24. Rodgers RG, Cole JC. The elevated plus-maze: phar- macology, methodology and ethology. In: Cooper SJ, Hendrie CA, eds. Ethology and Psychopharmacology. New York: John Wiley & Son Ltd, 1994: 9–44. 25. Volodin BYu. Potentialities of psychotherapy in onco- logical care. Rus J Oncol 2009; 1: 43–5 (In Russian). Copyright © Experimental Oncology, 2011