{"id":27457,"date":"2019-06-25T10:02:14","date_gmt":"2019-06-25T10:02:14","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=27457"},"modified":"2020-04-23T05:32:47","modified_gmt":"2020-04-23T05:32:47","slug":"lycopene-treatment-transposed-antidepressant-like-action-in-rats-provoked-to-chronic-mild-stress","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol12no2\/lycopene-treatment-transposed-antidepressant-like-action-in-rats-provoked-to-chronic-mild-stress\/","title":{"rendered":"Lycopene Treatment Transposed Antidepressant-Like Action in Rats Provoked to Chronic Mild Stress"},"content":{"rendered":"

Introduction\u00a0\u00a0\u00a0\u00a0\u00a0 <\/strong><\/p>\n

Depression\u00a0in\u00a0common\u00a0is\u00a0a psychiatric disorder, which\u00a0confers\u00a0a fourth prominent cause of disability\u00a0in worldwide by 2020. 1<\/sup> Its\u00a0prevalence\u00a0in an aged group is\u00a0considering, as of the\u00a0serious\u00a0psychiatric disorder, affecting up to 20%\u00a0of the world population. Characteristic features of marked\u00a0depression\u00a0are precisely mood\u00a0and sleep disturbances,\u00a0irritability\u00a0with an apparent loss of\u00a0pleasure\u00a0and\u00a0appetite.2\u00a0<\/sup>Depression is a disorder with a multifactor etiology that\u00a0includes\u00a0in\u00a0functional deficits in monoamines concentration and\u00a0disturbance in HPA-axis in inducing\u00a0 functional\u00a0and structural alterations in the brain.3,4<\/sup> CMS\u00a0model\u00a0of depression is precisely a valid model that inducing depression\u00a0in rodents, and mimics in\u00a0progress\u00a0in the depressive state\u00a0that had similar features in the human\u00a0depressive\u00a0state.5<\/sup> In this\u00a0model,\u00a0rats were inflicted\u00a0to a variety of stressor over a considerable period of\u00a0time, a gradual reduction in\u00a0intake\u00a0of sucrose and body weights with elevated serum corticosteroids that reflected by, a\u00a0decrease\u00a0in sensitivity to rewards namely (Anhedonia-loss of pleasure) is the most important symptom of\u00a0depression.6<\/sup> Decrease in the brain antioxidant enzyme activity and disturbances in HPA-axis is a major constraint factor, involved in processing emotional disorders like anxiety\u00a0and\u00a0depression.7<\/sup> Dysregulation in\u00a0HPA-axis\u00a0is associated, with induction of depression.8<\/sup><\/p>\n

Chronic stress brings about\u00a0structural changes in the hippocampus region that involved in regulating cognition.9<\/sup> Conventionally used antidepressants increase reuptake of monoamines which\u00a0crave\u00a02-4\u00a0weeks\u00a0to show antidepressant activity with 30% of remission. Currently used antidepressants show more incidences of side effects like cognition impairment, sexual and sleep disturbances and precipitation of seizures. There is\u00a0a\u00a0considerable need in developing newer\u00a0drugs with a lesser incident in potential side effects. Herbal drugs traditionally provide impressive scope in properly treating mood disorders with fewer adverse effects than synthetic compounds. Lycopene\u00a0an antioxidant widely distributed in various fruits and vegetables6<\/sup> and\u00a0highly lipid soluble and can readily cross the blood-brain barrier.10<\/sup> Existences of a \u03b2-ionic\u00a0ring in its structure show it as a potent antioxidant. Lycopene well recorded as it exhibits conservation against cancer and cardio vascular disease.11<\/sup> In according to\u00a0Zhang\u00a0et\u00a0al.,<\/em> studied\u00a0the antidepressant-like effect of lycopene in animal models by using lipid peroxidation for induction of depression.12<\/sup> In which author used a chemical method for induction of depression. In our\u00a0study, we used the natural method for inducing depression and widely expected model in inducing depression. we hypothesized that CMS model induce stress in animals and bring behavioral changes in rodent, we anticipating lycopene supplementation could be potent molecule that could able to\u00a0revert behavioral changes that are typically present during\u00a0the induction\u00a0of\u00a0stress.<\/p>\n

Materials and Methods<\/strong><\/p>\n

Animals<\/strong><\/p>\n

Male Wistar rats weighing between 240\u00b1 20 grams rats were housed 12hr light\/day cycle, under controlled temp\u00a0(22\u00b12c)\u00a0and humidity (40% -60%) with the standard chow feed and water were supplied at ad libitum<\/em> throughout the procedure. (IAEC\/52\/ SRU\/ 563\/2017)(Sri Rama Chandra Institute of Higher Education and Research, Chennai India).All the test was conducted as per CPCSEA guidelines.<\/p>\n

Drugs Administration and CMS Experimental Design<\/strong><\/p>\n

Imipramine\u00a0hydrochloride purchased from\u00a0sigma-aldrich and lycopene DC powder 10% product code LYP-03-C is obtained parry nutraceuticals. Lycopene is lipid soluble and it\u2019s dissolved in corn oil which acts as a vehicle for a drug administered orally once daily for 6-weeks. Lycopene at doses of 5mg\/kg,10mg\/kg, 20mg\/kg and standard drug imipramine\u00a0at a dose of 10mg\/kg.CMS and vehicle group received an equal volume of corn oil Control group will receive only saline water.<\/p>\n

CMS Protocol<\/strong><\/p>\n

On completion of acclimatization rodents was divided into two groups control\u00a0group and to-be\u00a0-stressed\u00a0group. A\u00a0control\u00a0group\u00a0is placed in a separate room which is free from contact with other stressor groups. And to-be\u00a0stressed group\u00a0is subjected, to a serious of stressor in an unpredictable manner to prevent dependence. The stressor includes.<\/p>\n

Food and Water Deprivation<\/strong><\/p>\n

(A separate periods of food and water deprivation, and one period of both food and water deprivation).<\/p>\n

Cage Tilting<\/strong><\/p>\n

Tilt the cages backward (~ 45 degrees).<\/p>\n

Soiled Cage<\/strong><\/p>\n

In which\u00a0250 ml plain water is poured into the sawdust.<\/p>\n

Grouped Housing<\/strong><\/p>\n

In which randomly changing the partners.<\/p>\n

Intermittent illumination<\/strong><\/p>\n

Switch the room lights on and off every ~ 2hr).<\/p>\n

Chronic Mild Stress<\/strong><\/p>\n

Wistar\u00a0rats were transfer into the experimental room a week proceeding to initiate the experiment. Animals were fasted for 14\u00a0hours\u00a0before conducting a consumption test rats are expose to a palatable 1%\u00a0sucrose\u00a0solution (100grams of sucrose dissolved in 100ml) for one\u00a0hour at the\u00a0end of\u00a0the session\u00a0bottles\u00a0are weighed, reduction in bottle\u00a0weight\u00a0gives\u00a0an amount of sucrose\u00a0consumed.CMS and vehicle groups are subjected to variety of stressor continuously for six weeks. Each stressor last for 10-14 hrs.<\/p>\n

Table 1: Experimental Design.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
S.no<\/strong><\/td>\nExperimental group<\/strong><\/td>\nDose <\/strong><\/td>\nNo. of animals <\/strong><\/td>\n\u00a0Treatment <\/strong><\/td>\n<\/tr>\n
1<\/td>\nControl<\/td>\nSaline<\/td>\n6<\/td>\nNo Stress<\/td>\n<\/tr>\n
2<\/td>\nCMS<\/td>\nSaline<\/td>\n6<\/td>\nStress<\/td>\n<\/tr>\n
3<\/td>\nCMS +Vehicle<\/td>\nCorn oil<\/td>\n6<\/td>\nStress + vehicle<\/td>\n<\/tr>\n
4<\/td>\nCMS +Impramine<\/td>\n10mg\/kg bw-1<\/td>\n6<\/td>\nStress + Treatment<\/td>\n<\/tr>\n
5<\/td>\nCMS +Lycopene<\/td>\n5mg\/kg bw-1<\/td>\n6<\/td>\nStress + Treatment<\/td>\n<\/tr>\n
6<\/td>\nCMS+Lycopene<\/td>\n10mg\/kg bw-1<\/td>\n6<\/td>\nStress + Treatment<\/td>\n<\/tr>\n
7<\/td>\nCMS+Lycopene<\/td>\n20mg\/kgbw-1<\/td>\n6<\/td>\nStress + Treatment<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Behavioral Test<\/strong><\/p>\n

Sucrose Preference Test(SPT)<\/strong><\/p>\n

Sucrose consumption test was performed as earlier described by.13<\/sup> In this test rodents were deprived of food and water 14 hrs before the sucrose preference test. Wistar rats were trained to consume\u00a0(1%)\u00a0palatable sucrose solution and water in individual bottles ad libitum<\/em> in each cage for a period of one hour. The consumption volumes of sucrose solution and water were recorded and calculated.13<\/sup><\/p>\n

Forced Swim Test (FST)<\/strong><\/p>\n

Forced swim test was conducted in an extensions glass cylinder of(height 40\u00a0cm\u00a0and diameters of 20 cm,) filled with water maintained at a Temp\u00a0(22-23\u00b0C)\u00a0at a depth of 30\u00a0cm. FST\u00a0activity was videotaped for 7 minutes. Initial 2 minutes of activity is discarded and the last 5 min of immobility was recorded and analyzed.\u00a0Increase in duration\u00a0of immobility in rats was regarded and more likely presented with depression-like state.14<\/sup><\/p>\n

Open\u00a0Field\u00a0Test\u00a0(OFT)<\/strong><\/p>\n

In open field test is used in screening, and assessing anxiety and exploratory behavior in rats.15<\/sup> Exploratory behavior task was documented for five min and following activities were recorded a.) Ambulation behavior b) Rearing behavior number of times rodents stood on its hind legs, which measures locomotor activity and anxiety c) Grooming behavior rodents spend time itching itself while in standing position increased incidence of grooming is an indicator of anxiety.16<\/sup> The test was conducted in a semi -dark room of low light (45 W fluorescent lights) and apparatus painted with black floor divided into 16 squares of equal sizes and lines with the white colour of 6 mm.<\/p>\n

Elevated Plus Maze (EPM)<\/strong><\/p>\n

In elevated plus maze test is used in screening\u00a0anxiety\u00a0in\u00a0rodents which show a naturally aversion\u00a0to\u00a0open spaces. It consists of two arms of opened and closed with dimensions of (45\u00a0\u00d7 10\u00a0\u00d7 0.5 cm) and (45\u00d710\u00d730 cm) respectively, positioned appositively to each other connected to a central platform of a dimension (10\u00a0\u00d7 10 cm)\u00a0and elevated 60 cm above the floor during a state of anxiety, rodents\u00a0tend\u00a0to move more towards the closed arm. Anti-anxiety treated rodents groups tend to move towards the open arm. Rats from each group were placed at the center of the maze, and activities were videotaped for 5 min activities like number of entries and duration of time spent in arms were recorded.16<\/sup><\/p>\n

Statistical Analysis<\/strong><\/p>\n

The results were expressed as Mean\u00b1S.D. Data were analyzed and differences between the means were determined by one-way ANOVA followed by Tukey\u2019s multiple comparisons post hoc analysis<\/em>. Using graph pad prism version 5.03 statistical software. In all the tests, differences were considered significant if p<0.05, to be a statistical significant.<\/p>\n

Result<\/strong><\/p>\n

Sucrose Preference Test<\/strong><\/p>\n

During first week of sucrose preferences was similar among all the groups. At the end of 6-week there is a statistical significance differences in sucrose intake between groups were noted i.e. Control vs.CMS group.CMS group rats preferred less intake of sucrose than control group (i.e CMS 40% -50% and control group 60% to 62%) (P<0.05). Lycopene treated groups showed an increase in intake of sucrose in comparison with CMS.There was no statistically significant differences in sucrose consumption among lycopene treated group were noted. Figure 1.<\/p>\n

Forced Swim Test<\/strong><\/p>\n

In our study CMS group display a significant increased in immobility time in contrast with control group[F(6,35)=10.08(p<0.01) there was no significant variation in immobility time between lycopene supplementation at 5mg\/kg and CMS group [F(6,35)=10.08(p>0.05). More over, supplementation of lycopene at10mg\/kg and 20mg\/kg could able to reduce immobility time when compared to CMS group [F(6,35) = 10.08 (p<0.01) in comparison to CMS group. Results are tabulated in. Table 2.<\/p>\n

Elevated Plus Maze<\/strong><\/p>\n

There is a significant difference in open arm entries between the control group versus CMS group[F(6,35)= 6.865],(p<0.05) and similarly, in closed arm entries in control group versus CMS group [F(6,35)=4.871],(p<0.05) respectively. However, lycopene treatment at 5mg, could not able to show any statistical significance in comparison to the CMS group (p>0.005). Lycopene dose of 20mg\/kg showed a significantly increased number of entries in open arm in comparison to the CMS group. Results are tabulated in Table 3.<\/p>\n

Open Field Test<\/strong><\/p>\n

CMS group rats showed anxious behavior in comparison with the control group by decreasing central square entries which is statistical significant [F(6,35)=15.56] (p<0.01) and also showed a significant difference by increasing grooming [F(6,35)=8.770] and duration of immobility time in comparison with the control group (p<0.01).However, supplementation, of lycopene could significantly reverse these changes by decreasing the immobility period. lycopene at a dose of 20mg\/kg could able to show anxiolytic activity. Results are tabulated in Table 4.<\/p>\n

Figure 1: Effect of lycopene and imipramine treatments on open field test in control and CMS-treated rats.<\/p>\n\n\n\n
\"Figure<\/td>\nFigure 1: Effect of lycopene on CMS induced rat subjected to sucrose preference test.<\/strong><\/p>\n

 <\/p>\n

Click here to view figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Data represents the mean \u00b1 S.D (n=6). Significance Was determine by one-way ANOVA followed by Tukeys test, #p<0.05 versus Control, *p<0.05 versus CMS.<\/p>\n

Table 2: Effect of lycopene and imipramine treatments on forced swim test in control and CMS-treated rats.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
S.no <\/strong><\/td>\nGroups <\/strong><\/td>\nDuration of immobility in (sec)<\/strong><\/td>\n<\/tr>\n
1<\/td>\nControl<\/td>\n79.0\u00b16<\/td>\n<\/tr>\n
2<\/td>\nCMS<\/td>\n96.7\u00b16**<\/td>\n<\/tr>\n
3<\/td>\nCMS+vehicle<\/td>\n96.8\u00b18*<\/td>\n<\/tr>\n
4<\/td>\nCMS+IMP 10mg\/kg<\/td>\n79.5\u00b15 ##<\/td>\n<\/tr>\n
5<\/td>\nCMS+LYP 5mg\/kg<\/td>\n92.6\u00b15<\/td>\n<\/tr>\n
6<\/td>\nCMS+LYP10mg\/kg<\/td>\n84\u00b17 #<\/td>\n<\/tr>\n
7<\/td>\nCMS+LYP 20 mg\/kg<\/td>\n82\u00b14 ##<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Tables 2: Effect of lycopene on chronic mild stress induced rats subjected to forced swim test Data are expressed as Mean \u00b1 SD. (n=6) statistical significance were determined by one way ANOVA followed by Tukey’s<\/em>** p<0.01,*p< 0.05 versus control and ## p<0.01, # p< 0.05 versus CMS.<\/p>\n

Table 3: Effect of lycopene and imipramine treatments on elevated plus maze test in control and CMS-treated rats.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
<\/td>\n<\/td>\n<\/td>\n\u00a0Number of entries to<\/strong><\/td>\n<\/tr>\n
S.no<\/strong><\/td>\n\u00a0Groups<\/strong><\/td>\nDefecation <\/strong><\/td>\nOpen arm entry<\/strong><\/td>\nClosed arm entry<\/strong><\/td>\n<\/tr>\n
1<\/td>\nControl<\/td>\n1.0\u00b10.3<\/td>\n3.8\u00b10.3<\/td>\n1.1\u00b10.7<\/td>\n<\/tr>\n
2<\/td>\nCMS<\/td>\n2.0\u00b10.3<\/td>\n1.6\u00b10.9*<\/td>\n3.1\u00b10.7*<\/td>\n<\/tr>\n
3<\/td>\nCMS + vehicle<\/td>\n2.2\u00b10.2<\/td>\n1.8\u00b11.0<\/td>\n2.8\u00b10.7<\/td>\n<\/tr>\n
4<\/td>\nCMS+IMP10mg\/kg<\/td>\n1.1\u00b10.2<\/td>\n3.6\u00b10.9 #<\/td>\n1.6\u00b11.2 #<\/td>\n<\/tr>\n
5<\/td>\nCMS+LYP 5mg\/kg<\/td>\n1.5\u00b10.3<\/td>\n2.6\u00b11.3<\/td>\n3.0\u00b10.6<\/td>\n<\/tr>\n
6<\/td>\nCMS+LYP10mg\/kg<\/td>\n1.2\u00b10.4<\/td>\n3.5\u00b10.7#<\/td>\n1.6\u00b11.0<\/td>\n<\/tr>\n
7<\/td>\nCMS+LYP20 mg\/kg<\/td>\n1.0\u00b10.2<\/td>\n3.6\u00b10.7 ##<\/td>\n1\u00b10.6 #<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Tables 3: Effect of lycopene on chronic mild stress induced rats subjected to elevated plus maze test.Data are expressed as Mean \u00b1 SD.(n=6)statistical significance were determined by one way ANOVA followed by Tukey’s<\/em>** p<0.01,*p< 0.05 versus control and ## p<0.01,# p< 0.05 versus CMS<\/p>\n

Table 4: Effect of lycopene and lmipramine treatments on open field test in control and CMS-treated rats.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong><\/td>\nOpen Field Exploratory Tests<\/strong><\/td>\n<\/tr>\n
S. no.<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Groups<\/strong><\/td>\nCentral square entries<\/strong><\/td>\n\u00a0Rearing<\/strong><\/td>\nGrooming<\/strong><\/td>\nDuration of immobility in sec<\/strong><\/td>\n<\/tr>\n
1<\/td>\nControl<\/td>\n5.5\u00b11.3<\/td>\n8.3\u00b1 0.8<\/td>\n2.1\u00b11.1<\/td>\n49.0\u00b112.4<\/td>\n<\/tr>\n
2<\/td>\nCMS<\/td>\n2.3\u00b11.2**<\/td>\n4.1\u00b12.0**<\/td>\n4.2\u00b11.2*<\/td>\n92.8\u00b118**<\/td>\n<\/tr>\n
3<\/td>\nCMS + vehicle<\/td>\n1.8\u00b11.1 **<\/td>\n4.1\u00b12.4*<\/td>\n4.6\u00b11.3*<\/td>\n109.0\u00b127*<\/td>\n<\/tr>\n
4<\/td>\nCMS+IMP 10mg\/kg<\/td>\n8.0\u00b11.7##<\/td>\n8.8\u00b10.7 ##<\/td>\n2.0\u00b11.6##<\/td>\n55.1\u00b113##<\/td>\n<\/tr>\n
5<\/td>\nCMS+LYP 5mg\/kg<\/td>\n3.3\u00b11.6<\/td>\n5.6\u00b12.4<\/td>\n4.8\u00b10.7<\/td>\n110\u00b122.4<\/td>\n<\/tr>\n
6<\/td>\nCMS+LYP10mg\/kg<\/td>\n3.0\u00b1 1.5<\/td>\n6.1\u00b12.7<\/td>\n2.3\u00b11.0<\/td>\n74\u00b118.0<\/td>\n<\/tr>\n
7<\/td>\nCMS+LYP20 mg\/kg<\/td>\n4.8\u00b11.6#<\/td>\n8\u00b11.6#<\/td>\n1.8\u00b11.1##<\/td>\n55\u00b19.9 #<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Tables 4: Effect of lycopene on chronic mild stress induced rats subjected to open field test. Data are expressed as Mean \u00b1 SD (n=6).Statistical significance were determined by one way ANOVA followed by Tukey’s<\/em>** p<0.01,*p< 0.05 versus control and ## p<0.01,# P< 0.05 versus CMS.<\/p>\n

Discussion<\/strong><\/p>\n

Chronic mild\u00a0stress\u00a0method\u00a0is the most\u00a0valid model used in inducing\u00a0depression\u00a0and in studying progressive behavioral changes in\u00a0rodents.17<\/sup>Chronic\u00a0stress\u00a0can provoke depression\u00a0and anxiety in\u00a0rodents.18<\/sup> In this procedure, rodents are subjected to\u00a0chronic\u00a0mild\u00a0stress\u00a0for 6-weeks. Behavioral\u00a0changes brought about during induction of\u00a0stress, were studied by conducting behavioral tests\u00a0like sucrose preference test,\u00a0forced swim test\u00a0and open field\u00a0test,\u00a0elevated plus maze\u00a0test\u00a0in\u00a0rodents.19<\/sup> Lycopene\u00a0is\u00a0a potent\u00a0antioxidant and\u00a0has\u00a0the highest antioxidant property among carotenoids. Lycopene doses were chosen in accordance with the previous studies (5mg\/kg,10mg\/kg and 20mg\/kg).20<\/sup> Rodents in a\u00a0state\u00a0of depressive-like behavior show more a\u00a0state\u00a0of immobility. This\u00a0immobility\u00a0state\u00a0can be successfully reversible with antidepressant drugs. 21<\/sup> In the present study, the CMS group showed an increase in the immobility time in comparison with the control group\u00a0these results\u00a0are consistent with the previous report.22,23<\/sup><\/p>\n

Lycopene treated\u00a0group\u00a0showed\u00a0an antidepressive like\u00a0activity\u00a0by decreasing immobility\u00a0time in\u00a0comparison\u00a0with the\u00a0CMS\u00a0group. In sucrose preference test there is a low consumption of sucrose solution, which\u00a0reflects the anhedonia\u00a0symptom\u00a0of\u00a0depression. During stress, rodents show aversion towards consumption of sucrose those activities can be reversed by antidepressant\u00a0 treatment.24<\/sup> CMS and vehicle groups showed a decrease in the consumption of sucrose which is reverted by lycopene treatment. Behavioral models like elevated plus maze and open\u00a0field tests\u00a0are commonly used in screening anxiety in rodents. Variables that can be determined during elevated\u00a0plus\u00a0maze that includes a\u00a0number\u00a0of\u00a0entries\u00a0in each\u00a0arm(i.e. open\u00a0arms and closed arms)25<\/sup> and also used\u00a0in\u00a0assessing\u00a0the anti-anxiety mechanism of action.26,27<\/sup> Previous studies are supporting the pharmacological validation of EPM with the use of anxiolytics like benzodiazepines, the effect of anxiolytic drugs is to cause an increase in the number of crossings onto the open arms of EPM and consequently reduce time spent in the closed arms of EPM. Lycopene supplemented groups\u00a0showed\u00a0a decrease in a number of\u00a0entries\u00a0in the closed\u00a0arm\u00a0and an increased number of\u00a0entries\u00a0in the open\u00a0arms. Table 3. Therefore, lycopene may be\u00a0considered\u00a0as an anxiolytic agent. It\u00a0showed\u00a0significant results at a dose\u00a0of 20mg\/kg.<\/p>\n

Open field test is used to study exploratory and anxiety behavior in rodents. Whose actives are\u00a0diminished\u00a0during chronic mild stress. Variables that can be determined in open field method like rearing, grooming, immobility time and central square entries. Increase in grooming and decrease in central square entries are the indicators of anxiety.28<\/sup> Grooming\u00a0rodents\u00a0spend time itching itself while in standing position increased grooming\u00a0and immobility time is\u00a0an\u00a0indicator\u00a0of\u00a0anxiety. Anxiolytic drugs like diazepam increase exploratory behavior, where as anxiogenic drugs like picrotoxin decrease exploratory activity. Lycopene supplementation dose of 20mg\/kg showed a significant number of entries into the central square versus the CMS group.Showed lycopene protection against the exploratory behavioral changes induced during induction of stress. Table 4: These results are comparable to the standard drug imipramine at a dose of 20 mg\/kg.<\/p>\n

Rearing the\u00a0number\u00a0of times\u00a0rodents\u00a0stood on its hind legs, a decrease in rearing activity shows a reduction in exploratory activity.28<\/sup> CMS group should a decreased rearing behavior in comparison with the control group.lycopene supplementation showed increased rearing behavior at a dose of 20mg\/kg.<\/p>\n

According to previous literature\u00a0lycopene showed the protective effect in\u00a0regulating\u00a0depressive-like behavior\u00a0induced by lipopolysaccharide, a\u00a0chemical\u00a0which\u00a0produces\u00a0neuro-inflammation in brain.29<\/sup> However,in this study, there is\u00a0a lack\u00a0of standard screening method for inducing depression. Lycopene supplemented dose of 5mg\/kg could not show, much alteration in any of behavioral models. Lycopene at a dose of 10mg\/kg showed a moderate response in forced swim test and elevated plus maze test, but did not show any significant response in open field method. Our data concluded that lycopene supplementation dose of 20mg\/kg has, anti-depressive activity and moderate anxiolytic activity. The standard drug imipramine showed antidepressant activity\u00a0and anxiolytic\u00a0activity\u00a0by increasing the proportionate number of entries in the open arm in the EPM test. Similarly, the duration of\u00a0mobility\u00a0and preference in sucrose consumption are increased in FST and SPT respectively indicates that\u00a0imipramine reversed stress-induced behavioral alterations.<\/p>\n

During lycopene supplementation of 6-weeks, there is no adverse effects were noted in rodents. Since lycopene doses were selected at a minimum dose. It was proved that lycopene dose of (3g\/kg.d)to be the safest dose in rodents.30<\/sup> These study findings have concluded that multifactorial event in the brain during the induction of stress, which might progress into neurodegenerative changes in the brain that manifested in the behavioral model. The\u00a0strength\u00a0of this\u00a0study\u00a0is that use of the most valid method in inducing depression.<\/p>\n

Conclusion<\/strong><\/p>\n

Study protocol, could successfully adeptly induce\u00a0depression\u00a0and anxiety-like activity in\u00a0rodents. Lycopene treatment could able to successfully reverted this condition because of its antioxidant activity and lipid soluble in nature, which can readily cross the blood -brain barrier which might improve the CNS functions. Further studies may be needed to elucidate the\u00a0possibility\u00a0of its\u00a0mechanism of\u00a0action.<\/p>\n

Conflict of Interest<\/strong><\/p>\n

There is no conflict of interest.<\/p>\n

Acknowledgements<\/strong><\/p>\n

The authors extend their thanks to Dr. Yogeshkumar Murkunde(veterinarian pathologist) and Balaji sravani Research Assistant CEFT, Sri Ramachandra Institute Of Higher Education And Research, Chennai, India, for helping in research work.<\/p>\n

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