Involvement of Potassium Channels and Monoaminergic Systems in ...

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701_____________________________________________Research ArticleInvolvement of Potassium Channels and Monoaminergic Systems in theAntidepressant Like Effect of Selegiline And Amiodarone in MicePV. Mhatarmare, VJ. Chaware and KR. BiyaniAnuradha College of Pharmacy, Anuradha Nagar, Sakegaon Road, Chikhli, Dist. Buldana,Maharashtra, India.ABSTRACTThe present study was taken up to investigate the effect of selegiline and amidarone on depression in mice. TheMAO-B inhibitor selegiline 100 mg/kg, p.o. and potassium channel blocker amidarone 100 mg/kg, p.o. wasadministered for seven days to albino mice (either sex) and evaluated for antidepressant like activity using Forcedswimming test (FST) and Tail suspension test (TST). Selegiline in higher dose loses it’s specificity and inhibit MAO-Aresults in increase in 5HT level elicited the antidepressant like activity in FST and TST by decreasing immobility timewhile amidarone elicited antidepressant like activity in FST and TST by blocking potassium channel decreases theimmobility time. This study investigates involvement of potassium channel and MAO system in the antidepressantlike effect of amidarone and selegiline in mouse FST and TST. The present study suggested that selegiline andamidarone possesses potential antidepressant effect which could be therapeutic interest for using in treatment ofpatient with depressive disorders.Key Words: Force swim test, Tail suspension test, Selegiline, Amiodarone, Monoaminooxidase, Serotonin.INTRODUCTIONDepression is an incapacitating psychiatric disease 1 . And the core symptoms include depressed mood, anhedonia(reduced ability to experience pleasure from natural rewards), irritability, difficulties in concentrating, andabnormalities in appetite and sleep etc 2 . Mental depression represents a major public health problem worldwide.The high prevalence of suicide in depressed patient upto 15% coupled with complication arising from stress and itseffect on cardiovascular system have suggested that it will be second leading death by the year 2020 3 . 20% ofpopulation in USA has been estimated to suffer from some depressive symptoms 4The main biochemical theory of depression is the monoamine hypothesis which states that the depression is causedby functional deficit of monoamines (NE, serotonin, and dopamine) at a certain sites in the brain. Reducedmonoaminergic signaling has been thought to underline depressive disorder. E.g. reduced monoamine metabolitelevel has been found in CSF of the depressed individual like wide serotonin, NE or DA. Depletion exertsprodepressive effects 5 . The MAO found in nearly all tissues and exists in two forms MAO-A and MAO-B and ismain target for antidepressant monoaminoxidase inhibitor. MAO responsible for metabolizing monoamines likeNE, DA, 5HT and MAO-B is substrate preference for phenylethylamine. Both the enzymes act on NE and DA. Indepression level of monoamine oxidase enzyme in brain increases which in turn reduces the level of monoamines 6 .The opening of K+ channels leads to hyperpolarization of cell membranes, which results in a decrease in cellexcitability 6 . Moreover, evidence indicates that antidepressants may modulate neuronal excitability via K + channelinhibition, and this may even be a common pathway of pharmacological action of these drugs. Studies havesuggested the involvement of K + channels in the modulation of depression. In fact, different types of K + channelinhibitors, such as tetraethylammonium (TEA), apamin, charybdotoxin, gliquidone and glibenclamide, were able toproduce an antidepressant like effect in the mouse FST 7, 8 . whereas the K + channel openers, such as minoxidil orcromakalim, increased the immobility time, indicating the induction of a depressant like effect 7 . Moreover, theblockade of K + channels enhances the basal release of 5-HT in rat hippocampal slices 9. Therefore the present studyattempt to investigate whether the different types of potassium channel and monoaminergic system are involved inantidepressant like activity of synthetic drugs like Potassium channel blocker and monoamino oxidase inhibitorrespectively.MATERIALS & METHODSProcurement of drugs and chemicals:1%Sucrose Solution, Imipramine, Amiodarone and Selegiline were procured from well known organization.Vol. 3 (4) Oct- Dec 2012 www.ijrpbsonline.com 1411

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701ANIMALSMale albino mice (25-30gm) ware procured from Animal House of Anuradha College of Pharmacy Chikhli, (Dist-Buldana). & were fed a standard diet, water was provided ad libitum & they will be acclimated 7 days before entryinto subsequent study. The protocol was approved by Institutional Animal Ethics Committee (IAEC).METHOD1. FORCED SWIMMING TESTThe forced swimming test employed was similar to that described previously 10, 11 .(Porsolt et al., 1977; Porsolt et al.,1978) Briefly, mice performed a swimming stress session for 15 min (pre-test), 24 h before being individuallyplaced in glass cylinders (height: 25 cm; diameter: 10 cm; containing 10 cm of water at 24±1 °C) for 6 min (test). Amouse was judged to be immobile when it cease struggling and remain floating motionless in the water, makingonly small movements necessary to keep its head above water. The duration of observed immobility was recordedduring the last 4 min of the 6-min testing period.2. TAIL SUSPENSION TESTThe tail suspension test was based on the method of Steru et al. (1985). Animals were suspended 50 cm above thefloor by means of an adhesive tape, placed approximately 1 cm from the tip of the tail. The time during which miceremain immobile was quantified during a test period of 6 min. Mice was considered immobile only when they hangpassively and completely motionless.Experimental DesignAnimals will be divided into four groups and each group contains 6 animals.Group I (Normal control) received vehicle, Group II (Standard group) received drug Imipramine 15mg/kg p.o.Group III and IV received Selegelline 100mg/kg and Amiodarone 100mg/kg p.o. respectively.Statistical analysisThe mean±S.E.M. values were calculated for each group. The data were analysed using one-way ANOVA followedby Dunnet’s multiple comparison test. P< 0.05 was considered to be statistically significant.RESULTS AND DISCUSSIONRESULTSForce swim test (FST)Results were given in table 1. A significant (P

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701Studies have suggested the involvement of K+ channels in the modulation of depression. In fact, different typesof K+ channel inhibitors, such as tetraethylammonium(TEA), apamin, charybdotoxin, gliquidone andglibenclamide, were able to produce an antidepressantlike effect in the mouse FST, whereas the K+ channelopeners, such as minoxidil or cromakalim, increased the immobility time, indicating the induction of adepressant like effect 7 (Galeotti et al.1999).CONCLUSIONIn the present study depression were evidenced by measurements of Immobility time and latency period in TST& FST that coincide with the observations of other investigator .The control animal resulted in increase inimmobility time in TST & FST. This effect was indicated by Earlier experimental findings have suggested thatthe Immobility parameters was involved in Depression because of their changes from normal. Our studydemonstrates the decrease in immobility time and increase in latency period by selegiline and amiodaronecontributes for antidepressant activity.Table 1: Effect of test drugs on immobility time in Force swim testTreatment for 7daysNo. ofAnimalsDosemg/kgLatency periodin secImmobilitytime in secI Control 06 10ml 83.50+1.17 145.83+3.96II Imipramine 06 15 181.83+0.65 53.33+0.66*III Selegiline 06 100 185.66+0.71 26.83+1.07*IV Amoidarone 06 100 138.00+0.73 61.50+1.33*Test Drugs were administered orally for 07 days prior to the test.Values represented mean±S.E.M. (n=6), *P

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-370112. Porsolt, R.D., Bertin, A., Jalfre, M., Behavioural despair in rats and mice: strain differences and the effectsof imipramine, Eur. J. Pharmacol. 1978; 51 :291–294.13. Steru, L., Chermat, R., Thierry, B., Simon, P., The tail suspension test: a new method for screeningantidepressants in mice, Psychopharmacology. 1985; 85 : 367–370.14. Bolotina VM., Najibi S., Palacino JJ., Pagano PJ., Cohen RA., Nitric oxide directly activates calciumdependentpotassium channels in vascular smooth muscle, Nature. 1994; 368 (6474) :850–853.Vol. 3 (4) Oct- Dec 2012 www.ijrpbsonline.com 1414