{"id":28413,"date":"2019-09-25T10:58:38","date_gmt":"2019-09-25T10:58:38","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=28413"},"modified":"2020-04-22T10:23:07","modified_gmt":"2020-04-22T10:23:07","slug":"effect-of-duloxetine-pretreatment-on-5-htp-and-dexfenfluramine-induced-behaviours-in-albino-rats-2","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol12no3\/effect-of-duloxetine-pretreatment-on-5-htp-and-dexfenfluramine-induced-behaviours-in-albino-rats-2\/","title":{"rendered":"Effect of Duloxetine Pretreatment on 5-Htp and Dexfenfluramine Induced Behaviours in Albino Rats"},"content":{"rendered":"

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

The stimulation of central brain serotonergic receptors viz 5-HT1A<\/sub> and 5-HT2A <\/sub>\u00a0, induces the serotonergic behaviours in rats characterized by lateral head weaving, forepaw treading, hind limb abduction, flat body posture, straub tail and wet-dog shakes1,2,3<\/sup>. This serotonergic behaviours can be induced by drugs like 5-HT precursors viz tryptophan, 5-hydroxytryptophan 4,5,6<\/sup>, 5-HT releasers like dexfenfluramine, p-chloroamphetamine (PCA) which selectively release neuronal 5-HT7,8,9<\/sup> and 5-HT receptor agonists10,11,12<\/sup>\u00a0 which stimulate 5-HT1A<\/sub> and 5-HT2A<\/sub> receptors. This behavioural syndrome induced by 5-HT has been scored by different methods on the basis of rating scales for its components3,11,12,13<\/sup>.<\/p>\n

This study has investigated the behavioural effects of 5-HTP and dexfenfluramine in rats pretreated with different doses of duloxetine and scored by scoring method of Sloviter et al3<\/sup>.<\/p>\n

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

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

Male and female albino rats weighing 100-200 gm were used for experiments. Animals used for the experiments were bred in Central Animal House of the Institute. The animals were kept under standard conditions, maintained on a 12 hr light\/dark cycle and they were given food and water ad libitum till the time of experimentation. The rats were brought to the experimental area at least 1 hr before the experimentation. Experimental design consisted of 8 groups of fresh rats ( n = 6 in each group). All observations were made blind with respect to the treatments used. The experimental protocol was reviewed and approved by the Institutional Animal Ethics Committee and carried according to the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines<\/p>\n

Drugs<\/strong><\/p>\n

Duloxetine (Macleod), dexfenfluramine hydrochloride (Wockhardt), 5 – hydroxytryptophan (Sigma) were used in pure powder form. Fresh drug solutions were prepared by dissolving drug in distilled water (DW). Drugs were injected intraperitoneally and injection volume was 2 ml\/kg body weight. Dose selection was done on the basis of literature and past studies carried out in our department.<\/p>\n

Effect of Duloxetine Pretreatment on Behavioral Syndrome Induced by\u00a0 5-HTP and Dexfenfluramine (DEX) In Rats.<\/strong><\/p>\n

Animals were placed separately in perspex cage. They were individually observed as per the method of Sloviter et al3 <\/sup>for 1 min, once after every 5 min, from 10 to 125 min timing after injection of 5-HTP and DEX for 20 scoring periods. Serotonergic behaviours observed were head and whole body shakes, reciprocal forepaw treading, lateral head weaving, flat body posture and hind limb abduction. Animals were scored separately (0 or 1) in each of the twenty intervals for 1 min observation period. Total score of each animal in the group for every scoring period was taken and the mean value of the group calculated. Control group (DW 2 ml\/kg i.p.) and test group ( duloxetine 5,10,20 mg\/kg) received the drug one hour before receiving 5-HTP\/DEX.<\/p>\n

Effect of Duloxetine pretreatment on 5-Hydroxytryptophan Induced Behaviour in Rats.<\/strong><\/p>\n\n\n\n\n\n\n\n
Groups<\/strong><\/td>\nTreatment used\u00a0 i.p mg\/kg<\/strong><\/td>\n<\/tr>\n
1.<\/td>\nDW (2 ml\/kg )\u00a0 + 5-HTP 75<\/td>\n<\/tr>\n
2.<\/td>\nDuloxetine 5 \u00a0\u00a0\u00a0\u00a0+ \u00a0\u00a05-HTP 75<\/td>\n<\/tr>\n
3.<\/td>\nDuloxetine 10 \u00a0\u00a0+ \u00a05-HTP 75<\/td>\n<\/tr>\n
4.<\/td>\nDuloxetine 20 \u00a0\u00a0+ \u00a05-HTP 75<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Effect of Duloxetine pretreatment on Dexfenfluramine Induced Behaviour in Rats.<\/strong><\/p>\n\n\n\n\n\n\n\n
Groups<\/strong><\/td>\nTreatment used i.p mg\/kg<\/strong><\/td>\n<\/tr>\n
1.<\/td>\nDW (2 ml\/kg )\u00a0 \u00a0+ \u00a0Dexfenfluramine 10<\/td>\n<\/tr>\n
2.<\/td>\nDuloxetine 5\u00a0\u00a0\u00a0 \u00a0+ \u00a0Dexfenfluramine 10<\/td>\n<\/tr>\n
3.<\/td>\nDuloxetine 10 \u00a0\u00a0+ \u00a0Dexfenfluramine 10<\/td>\n<\/tr>\n
4.<\/td>\nDuloxetine 20 \u00a0\u00a0+ \u00a0Dexfenfluramine 10<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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

Data was analysed by using Graph pad instat software. Non-parametric ANOVA,<\/p>\n

Kruskal Wallis test followed by post hoc Dunn\u2019s multiple comparison test was used .<\/p>\n

p < 0.05 \u00a0was considered\u00a0 statistically significant<\/p>\n

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

Effect of Duloxetine pretreatment on 5-HTP induced Behavioral Syndrome in Rats<\/strong><\/p>\n

As per table 1, 5-HTP treated control group rats showed the 5HT1A <\/sub>and 5HT2A<\/sub> receptor mediated behavioral syndrome. Pretreatment with 20 mg\/kg duloxetine potentiated the behavioral syndrome intensity induced by 5-HTP (75 mg\/kg) which is statistically significant. \u00a0Pretreatment with 5 & 10 mg\/kg did not influence behavioural syndrome induced intensity by 5-HTP (75 mg\/kg).<\/p>\n

Table 1: Effect of Duloxetine pretreatment on 5-HTP Induced Behaviour in Rats.<\/strong><\/p>\n\n\n\n\n
\n

Group<\/strong><\/p>\n

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

Testing Time Interval in (min)<\/strong><\/p>\n<\/td>\n

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

Control<\/strong><\/p>\n

+<\/strong><\/p>\n

5 \u2013 HTP<\/strong><\/p>\n

75<\/strong><\/p>\n

Mean \u00b1 SD<\/p>\n<\/td>\n

\n

Study Groups (mg\/kg)<\/strong><\/p>\n<\/td>\n

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

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

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

KW Value<\/strong><\/p>\n<\/td>\n

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

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

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

P Value<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

DUL5<\/strong><\/p>\n

+<\/strong><\/p>\n

5-HTP<\/strong><\/p>\n

75<\/strong><\/p>\n

Introduction The stimulation of central brain serotonergic receptors viz 5-HT1A […]<\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-28413","post","type-post","status-publish","format-standard","hentry","category-vol12no3"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/28413","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=28413"}],"version-history":[{"count":6,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/28413\/revisions"}],"predecessor-version":[{"id":31944,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/28413\/revisions\/31944"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=28413"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=28413"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=28413"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}