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616.89-07-08:005.745 (06) 56.14-4-5 ӻ, ISBN 978-985-558-002- ESSENTIAL CHARACTERISTICS OF INTEGRATIVE DEVELOPMENT OF INDIVIDUAL, PSYCHIC AND PROFESSIONAL HEALTH Verbina G.G., Kaplanova A.J................................................................................................... EFFECTS OF CONCOMITANT EXPOSURE OF DHE AND -CtxMII ON NICOTINE-EVOKED [3H]DOPAMINE OVERFLOW IN RAT STRIATAL SLICES Pivavarchyk M.V...................................................................................................................... INHIBITION OF NICOTINE-EVOKED [3H]DOPAMINE OVERFLOW BY TETRAKIS QUATERNARY AMMONIUM ANALOGS Pivavarchyk M.V...................................................................................................................... .., ................................................................................

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.......................................................................................................................... .............................................................................................................................. (, ) .., ......................................................................................... , 2005 ................................................................................................................. , .., .., ........................................................................... - ......................................................................................................................... , .., .............................................................................................. .., .., .., .., .............. .., .., .., ........................................... .., ..................................................................................... : ................................................................................................................ , .., ......................................................................................... : - .., .., .., ........................................... - ........................................................................................................................... , . ..................................................................................................................... , , ........................................................................................................................ .......................................................................................................................... .......................................................................................................................... ( ) .., .., .., ........................................... .., .., .., ............................... : ......................................................................................................................... , .......................................................................................................................... ............................................................................................................................... .............................................................................................................................. , , , ........................................................................................................................... .., . ., .., ...................... - .., ............................................................................................... .., ................................................................................................... - .., ................................................................................................. ............................................................................................................................ .., ......................................................................................... .., ............................................................................................... .., .., ................................................................... .., .., .................................................................... . ., . ., .., ..................................................... . .., .......................................................................................... ESSENTIAL CHARACTERISTICS OF INTEGRATIVE DEVELOPMENT OF INDIVIDUAL, PSYCHIC AND PROFESSIONAL HEALTH Verbina G.G., Kaplanova A.J.

Chuvash State University named after I.N. Ulyanov, Cheboksary, Russia Many foreign and domestic researchers concerned directly or indirectly the questions connected with a problem of individual, mental and professional health. Researchers not only described separate personal characteristics, formed in the process of individual, mental and professional improvement, but also addressed to search of a complete portrait of an ideally healthy person (K. Rogers, A. Maslou, F. Perlz, etc.).

Development and the essence of a personality with scale of time and space of all course of life are considered and connected with acmeological approach. On the basis of ac meological approach there is the idea of creation or integrity restoration.

The essential characteristic of integrative development of mental, individual and pro fessional health, in our opinion, consists of ensuring needs satisfaction of a person on condi tions and on the basis of its health conserving development, the state and functioning of orga nized internal and external systems and connections of an individual and society. Constantly developing totality of mental, individual and professional properties of a person provides harmony between needs of an individual and society, and focuses an individual on perfor mance of its vital task.

From our point of view, the essential characteristics of integrative development of in dividual, mental and professional health are: multilevelity, healthy adaptation and adaptabili ty, dynamism, activity.

The multilevelity is understood by us as a personal adaptable potential including vari ous health conserving levels: resistance to stress, self-appraisal of a personality, social sup port, valuable orientations, sociability, moral orientation, group identification, etc.

Healthy adaptation. Adaptation is the adaptation of a structure and functions of an organism, its organs and cells to the environment conditions, directed on homeostasis preser vation. The main types of adaptable process are formed depending on the structure of needs and motives of an individual: 1. the active type is characterized by the prevalence of active impact on the social environment and on itself;

2. the passive type is defined by passive, con formal acceptance of purposes and orientations of valuable groups. Adaptation efficiency es sentially depends on that, how adequately an individual perceives itself and its social roles and connections: distorted or insufficiently developed idea of itself results in adaptation viola tions, as extreme expression of that autism serves. Violations of adaptation also results in neu rotic and psychosomatic frustration, alcoholism, drug addiction and so forth.

Healthy adaptability is expressed, from our point of view, in purposeful functioning of the complete organism of an individual, defined by coordination and correspondence of its purposes and results reached during health conserving activity.

Dynamism. Dynamics is the process of development, changes of any phenomenon.

Dynamism in health conserving is understood by us as the basis of motive forces of individu al, mental and personal development increasing health conserving competence and leading to Acme.

Activity is the aspiration of a subject to leave out of its own limits, to expand a field of activity, to operate behind limits of requirements of a situation and role representations. The integrated characteristic of a healthy personality is the active living position directed on the development of health conserving competence and responsibility for health and life.

The direct relation to understanding of essential characteristics of integrative devel opment of individual, mental and professional health, in our opinion, is in the fundamental thesis of psychosynthesis that the aspiration to internal integration is among fundamental mo tives of a person;

but it doesnt mean that a personality is already an organic and harmonious ly functioning integrity. Without knowing and without understanding itself, a person doesnt operate itself, rotating in the circle of its mistakes and shortcomings. Difficulties of self knowledge and self-development result from inaccessibility to knowledge of true I, that is explained by the existence of two-unity of personal I and true I: the first sometimes doesnt realize the existence of the second and even denies its existence. Actually there are no two I, as two independent and isolated beings. There is I, which is shown at different le vels of consciousness and self-comprehension. Intuitively feeling itself as a whole and, never theless, finding in itself internal split, a person comes to confusion and cant understand neither itself nor others. The organic unity is the purpose of a person, but not its present condition. In especially favorable conditions the finding of internal unity is the result of spontaneous growth and maturing, in other cases it is a merited reward received thanks to work on itself, to education or psychocorrection with application of special methods, which facilitate and accelerates the process of self-control, self-development and self-realization, that well influences on the integrative development of individual, mental and professional health.

The researches carried out by us confirm that the organism is trustworthy and is much more capable to self-defense and to self-control, than it is considered to be. Various workings out showed the theoretical need to postulate a certain sort of positive development or tenden cy to self-actualization of an organism which differs similarly both from aspiration to preser vation, maintenance in an equilibrium state and homeostatic process, and from tendency of an organism to react to impulses from the outside world Thus, it is possible to say that the essence of integrative development of individual, mental and professional health, and also its conservation and strengthening is concluded in self-knowledge, the activity of living position, self-control, self-organizing, self-realization, self-actualization, self-development and self-improvement.

Literature 1. Abulkhanova-Slavsky K.A. Strategy of Life. Moscow: Myusl, 1991. 299 pages.

2. Rogers K. View of Psychotherapy: transl. from English // Formation of a Person / gen. edition and preface E.I. Isenina. Moscow, 1994. 480 pages.

3. Perlz F. Workshop on a Geshtalttherapy. Moscow, 2001. 228 pages.

EFFECTS OF CONCOMITANT EXPOSURE OF DHE AND -CTXMII ON NICOTINE-EVOKED [3H]DOPAMINE OVERFLOW IN RAT STRIATAL SLICES Pivavarchyk M.V.

Yanka Kupala State University, Grodno, Belarus Tobacco smoking is the main cause of preventable morbidity in the world. Pharmaco therapy can be useful to achieve long-term abstinence. Pharmacotherapy must provide suc cessful treatment of tobacco dependence and withdrawal, and thereby facilitate efforts to get and prolong tobacco self-control. The most important alkaloid in tobacco, nicotine, activates a few subtypes of nicotinic receptors (nAChRs) which enlarge brain extracellular dopamine (DA) producing nicotine reward leading to addiction. nAChRs are located primarily presy naptically and modulate synaptic activity by regulating dopamine release. Subtype-selective nAChR antagonists that block reward-relevant mesocorticolimbic and nigrostriatal DA release induced by nicotine may offer advantages over existing therapy for smoking cessation. Only a few sybtype-selective antagonists are currently available for use as pharmacological tools to investigate the physiological roles of specific nAChRs. One of them is -Conotoxin MII ( CtxMII), which binding remains in brain from 3 knockout mice, but is abolished in knockout mice [1], [2], indicating that -CtxMII binds to 6-nAChR subtypes. Other data suggest that 6-nAChRs may offer a powerful molecular target for a highly selective harma cotherapeutic strategy to combat nicotine addiction [3].

The purpose of the current study was to determine if 42 nicotinic receptor antagon ist dihydro--erythroidine (DHE) interacts with -CtxMII (-conotoxin MII)-sensitive nAChRs. The maximal concentrations were based on the previously determined Imax value for analog and -CtxMII- induced inhibition of nicotine-evoked [3H]DA overflow in rat striatal slices. Inhibition of the effect of nicotine by the DHE alone as well as in combination with -CtxMII was determined. Rat striatal slices were incubated for 30 min in Krebs buffer (118 mM NaCl, 4.7 mM KCl, 1.2 mM MgCl2,1.0 mM NaH2PO, 1.4 mM CaCl2, 11.1 mM glucose, 25 mM NaHCO3, 0.11 mM L-ascorbic acid and 0.004 mM disodiumethylenedia mine tetraacetate, pH 7.4, saturated with 95% O2/5% CO2) in a metabolic shaker for 30 min.

Slices were incubated with 0.1 M [3H]DA for 30 min, transferred to a superfusion chambers maintained at 34C (Brandel suprafusion system 2500) and were superfused for 60 min with oxygenated Krebs buffer containing both 10 M nomifensine (a DA uptake inhibitor) and M pargyline (a monoamine oxidase inhibitor), to prevent reuptake and metabolism of [3H]DA, respectively. Duplicate striatal slices were superfused for 36 min with maximally inhibitory concentrations of -CtxMII (1 nM) and DHE (10 M). Slices were then super fused with 10 M nicotine for an additional 36 min. Separate duplicate slices were also super fused with a maximally inhibitory concentration of mecamylamine (10 M) for comparison with a nonselective nAChR antagonist. At the end of the experiment, each slice was solubi lized, and the [3H]-content of the tissue and samples were determined by liquid scintillation spectroscopy.

T o ta l [3 H ]D A o v e r flo w 160 control -CtxMII DH E Fractional Release ( % c o n tr o l ) 140 DHBE+-CtxMII Mec (% basal) 120 Nicotine -CtxMII DH E DH E+ control Mec 44 52 60 68 76 -CtxMII Time (min) Fig. 1 Concomitant exposure of rat striatal slices to maximally effective concentrations of DHE and -CtxMII. Slices were superfused in the absence (control) or presence of 10 M mecamylamine (positive control), DHE, -CtxMII or -CtxMII + DHE for 36 min prior to nicotine addition to the buffer;

superfusion continued for 36 min with nicotine added to the buffer. Control represents [3H]DA overflow in response to 10 M nicotine as a percent of tis sue [3H]content, mean S.E.M, n = 5 rats. Left panel: time course of nicotine-evoked [3H]DA overflow in the absence and presence of DHE, -CtxMII or -CtxMII + DHE. Da ta are expressed as fractional release as a percent of basal outflow. Arrow indicates the time point at which nicotine was added to the superfusion buffer.

Current superfusion of rat striatal slices with maximally effective concentrations of DHE and -CtxMII resulted in significant inhibition of nicotine-evoked [3H]DA overflow compared to the within-subject control, i.e. nicotine-evoked [3H]DA overflow in the absence of the analogs. Importantly, inhibition of nicotine-evoked [3H]DA overflow resulting from concomitant exposure of DHE and -CtxMII was different (p 0.05) from that produced by either antagonist alone. The time course of the response to nicotine and antagonists shows clearly that the inhibition produced by the antagonists presented concomitantly was different from that following either DHE or -CtxMII alone (Fig. 1, left panel). A nonselective nAChR antagonist mecamylamine inhibit 90% of nicotine-evoked [3H]DA overflow. Thus, the current finding suggests that 42 nicotinic receptor antagonist dihydro--erythroidine and -CtxMII inhibit different subtypes of nAChRs. This analogs can be useful as pharmaco logical tools to investigate the physiological roles of specific 42 and 6-nAChRs.

References 1. Champtiaux N, Han ZY, Bessis A, Rossi FM, Zoli M, Marubio L. et al. Distribution and pharmacology of 6-containing nicotinic acetylcholine receptors analyzed with mutant mice. J Neurosci. 2002;

22:1208-1217.

2. Whiteaker P, Peterson CG, Xu W, McIntosh JM, Paylor R, Beaudet AL. et al. In volvement of the alpha3 subunit in central nicotinic binding populations. J Neurosci.

2002;

22:2522- 3. Exley R, Clements MA, Hartung H, McIntosh MJ, Cragg SJ. 6 Containing nicotin ic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens. Neuropsychopharmacology. 2008;

33:2158-2166.

ACKNOWLEDGEMENTS: This research was supported by USPHS Grant U19 DA INHIBITION OF NICOTINE-EVOKED [3H]DOPAMINE OVERFLOW BY TETRAKIS QUATERNARY AMMONIUM ANALOGS Pivavarchyk M.V.

Yanka Kupala State University, Grodno, Belarus Nicotine, the major psychoactive compound present in tobacco smoke, activates nico tinic acetylcholine receptors (nAChRs), and evokes dopamine (DA) release from presynaptic terminals in the mesolimbic and nigrostriatal dopamine pathways, leading to habitual tobacco use [1], [2]. A novel approach to developing effective tobacco cessation pharmacotherapies is to discover molecules that selectively inhibit acetylcholine receptors subtypes which mediate nicotine-evoked DA release [3].

In order to identify compounds with higher affinity and selectivity as nAChRs anta gonists, a series of tetrakis quaternary ammonium analogs, containing four quaternary ammo nium moieties connected to a central phenylene ring, were used in our experiments. The pur pose of the current study was to determine the concentration response of the tetrakis quaternary ammonium compounds (tkPIQB, tkP3HPPB, tkP3BzPB) to inhibit nicotine evoked [3H]dopamine release from rat striatal slices.

Rat striatal slices were incubated for 30 min in Krebs buffer (118 mM NaCl, 4.7 mM KCl, 1.2 mM MgCl2,1.0 mM NaH2PO, 1.4 mM CaCl2, 11.1 mM glucose, 25 mM NaHCO3, 0.11 mM L-ascorbic acid and 0.004 mM disodiumethylenediamine tetraacetate, pH 7.4, satu rated with 95% O2/5% CO2) in a metabolic shaker at 34C for 30 min. Slices were incubated with 0.1 M [3H]DA for 30 min, transferred to a superfusion chambers maintained at 34C (Brandel suprafusion system 2500) and were superfused for 60 min with oxygenated Krebs buffer containing both 10 M nomifensine (a DA uptake inhibitor) and 10 M pargyline (a monoamine oxidase inhibitor), to prevent reuptake and metabolism of [3H]DA, respectively, and to assure that the [3H] collected in superfusate primarily represented parent neurotrans mitter. Slices were superfused for 36 min in the absence (control) or presence of a single con centration of analog. Then, nicotine (10 M) was added to the buffer and slices were super fused for an additional 36 min in the absence (control) and presence of analog. At the end of the experiment, each slice was solubilized, and the [3H]-content of the tissue and samples were determined by liquid scintillation spectroscopy.

The ability of tetrakis-quaternary ammonium compounds to evoke [3H]DA overflow from superfused rat striatal slices preloaded with [3H]DA was determined across a range of analog concentrations (0.001 to 10 M), none of the analogs had intrinsic activity. Concentra tion response curves of tetrakis analogs (Fig. 1) show the concentration-dependent of the te trakis analogs-induced inhibition of the effect of nicotine. Maximal inhibition (Imax) was 66 2.2%, 50 3.3%, 84 6.7% for tkP3HPPB, tkPIQB tkP3BzPB, respectively. IC50 value ob tained for tkP3HPPB was 15.6 7.4 nM;

for tkPIQB 12779 nM and for tkP3BzPB 28.0 11.0 nM. For each analog, repeated measures one-way ANOVA revealed significant concen tration effect of nicotine-evoked [3H] DA overflow: tkP3HPPB, F7, 27 = 6.09, p 0.001;

tkPIQB, F7, 26 = 6.025, p 0.002;

tkP3BzPB, F6, 35 = 4.96, p 0.009.

Slices were superfused in the absence (control) or presence of analog for 36 min prior to nicotine addition to the buffer;

superfusion continued for 36 min with nicotine added to the buffer. Data are mean S.E.M. total [3H]DA overflow (% control), n = 4-6 rats/analog. Con trol represents [3H]DA overflow in response to 10 M nicotine as a percent of tissue [3H]content (2.30 0.38 fraction release). Curves for concentration response were generated by nonlinear regression.

tkPIQB Total [3H]DA Overflow tkP3HPPB tkP3BzPB (% Control) -9 -8 -7 -6 - Control Log [Analog] (M) Fig. 1 Concentration-dependent inhibition of nicotine-evoked [3H]DA overflow by te trakis-azaaromatic quaternary ammonium analogs Fig. 2 Chemical structure one of tetrakis-azaaromatic quaternary ammonium analog In current work full concentration response of tetrakis-quaternary ammonium analogs (tkPIQB, tkP3HPPB and tkP3BzPB) clearly shows that they are highly potent inhibitors of nicotine-evoked DA release. The effect of nicotine (10 M) was inhibited by tetrakis analogs in a concentration-dependant manner (IC50 = 15-127 nM). The incomplete maximal inhibition produced by the tetrakis analogs (Imax= 50 84%) can be evident that this compound didnt inhibit all types of nAChRs mediating nicotine-evoked DA release, indicating on their possi ble selectivity. Thus, the current finding suggests that tetrakis-quaternary ammonium analogs represent new structural scaffolds for discovery of a novel class of pharmacotherapies for smoking cessation.

References 1. Corrigall WA, Franklin KB, Coen KM and Clarke PB. The mesolimbic dopaminer gic system is implicated in the reinforcing effects of nicotine. Psychopharmacology (Berl).

1992;

107(2-3):285-289.

2. Govind AP, Vezina P and Green WN. Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction. Biochem Pharmacol.

2009;

78(7):756-65.

3. Dwoskin LP and Bardo M. Targeting nicotinic receptor antagonists as novel phar macotherapies for tobacco dependence and relapse. Neuropsychopharmacology. 2009;

34(1), 244-246.

ACKNOWLEDGEMENTS: This research was supported by USPHS Grant U19 DA ..1, ..

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60% (42) . 22 30 13 (18,6%) , 31-40 41-50 (27,1%);

51-60 12 (17,1%) 60 7 (10%) .

: - 81,4% (57), 7,1% (5);

10% (7);

1,4% (1).

. 70 .

AUDIT- . 17,1% (12) , , 54,3% (38) , 1 ;

22,9% (16) , 2-4 ;

3 (4,3%) , 2-3 1 , 4 .

AUDIT- . 62,9% (44) , 1- () (1 30 , 75 , 100 250 );

15,7 % (11) , 3-4 ;

10,0% 5-6 ;

4,3% (3) 7-8 .

AUDIT , 6 . 10% (7) , , 1 , ;

45,7% (32) , . 14,3% (10) , .

32,9% (23) : 46,4 % (13 28) 23,6% (10 42).

. , .

AUDIT- .



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