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Master's Dissertation
DOI
10.11606/D.59.2011.tde-23112011-110321
Document
Author
Full name
Lucas Canto de Souza
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2011
Supervisor
Committee
Mattioli, Rosana (President)
Medalha, Carla Christina
Zangrossi Junior, Helio
Title in Portuguese
Clorfeniramina microinjetada no hipocampo dorsal reverte e efeito ansiolítico da L-histidina e prejudica a memória emocional de camundongos
Keywords in Portuguese
Ansiedade
Clorfeniramina
Hipocampo dorsal
L-histidina
Memória emocional
Abstract in Portuguese
O nosso grupo tem investigado os efeitos da Clorfeniramina (CPA), antagonista H1, e da L-histidina (LH), uma droga precursora da síntese de histamina, sobre a ansiedade e a memória emocional. Diante disso, os objetivos desse estudo foram investigar os efeitos LH administrada i.p. e da CPA microinjetada no hipocampo dorsal sobre a ansiedade e a memória emocional de camundongos submetidos ao labirinto em cruz elevado (LCE). O experimento foi realizado em dois dias consecutivos. No primeiro dia (T1) 71 camundongos machos da cepa Suíço-Albino pesando 25-35g foram pré-tratados i.p. com salina (SAL) ou LH (500mg/Kg). Após duas horas, os sujeitos receberam microinjeção de SAL ou CPA (0,016nmol; 0,052nmol; 0,16nmol/0,1l) no hipocampo dorsal. Após cinco minutos, os animais foram expostos ao LCE por cinco minutos. Vinte quatro horas depois, o mesmo protocolo experimental foi adotado na reexposição (T2). Os animais foram distribuídos aleatoriamente em 8 grupos de acordo com o tratamento farmacológico: SAL/SAL (n=9), SAL/CPA1 (n=9), SAL/CPA2 (n=10), SAL/CPA3 (n=8), LH/SAL (n=10), LH/CPA1 (n=8), LH/CPA2 (n=8) e LH/CPA3 (n=9). As três doses de CPA microinjetadas no hipocampo dorsal não alteraram a porcentagem de tempo gasto nos braços abertos (%TBA) na exposição ao LCE: T1 SAL/CPA1 (46,13±4,45); SAL/CPA2 (47,59±4,89); SAL/CPA3 (44,30±6,65) quando comparados com o grupo controle SAL/SAL (35,84±2,77) e não alteraram o número de entradas nos braços fechados (EBF) SAL/CPA1 (8,56±1,06); SAL/CPA2 (9,70±1,10); SAL/CPA3 (9,38±1,25) - quando comparados com o grupo controle SAL/SAL (10,56±1,11). A administração i.p. de LH aumentou a %TBA em T1 para o grupo LH/SAL (59,79±4,71), quando comparado ao grupo controle SAL/SAL (35,84±2,77), mas não alterou o EBF: LH/SAL (9,20±1,78) e SAL/SAL (10,56±1,11). Os animais do grupo LH/CPA3 diminuíram %TBA (32,25±4,81) em T1 quando comparados com o grupo LH/SAL (59,79±4,71). Os animais do grupo SAL/CPA1 não apresentaram diminuição da %TBA em T2 (T1: 46,13±4,45; T2: 39,38±6,53). O mesmo foi observado para os sujeitos dos grupos LH/CPA2 (T1: 50,10±3,99; T2: 40,97±8,22) e LH/CPA3 (T1: 32,25±4,81; T2: 32,16±6,93). Nós concluímos que: a CPA microinjetada no hipocampo dorsal de camundongos não apresenta efeito sobre a ansiedade; a administração intraperitoneal de LH apresenta efeito ansiolítico em camundongos expostos ao LCE e que esse efeito é revertido pela maior dose de CPA (0,16nmol/0,1l); são necessárias maiores doses de CPA para que haja prejuízo na memória emocional de camundongos reexpostos ao LCE quando os níveis de histamina no hipocampo dorsal estão elevados.
Title in English
Dorsal hippocampal microinjections of chlorpheniramine reverses anxiolitic-like effect of L-histidine and impairs mice emotional memory.
Keywords in English
anxiety
Chlorpheniramine
dorsal hippocampus
emotional memory
L-histidine
Abstract in English
Our group has been investigating the effects of Chlorpheniramine (CPA), a histaminergic H1 antagonist, and of L-Histidine (LH), a histamine precursor, on anxiety-related behaviors and emotional memory. Thus the aim of this study was to investigate the effects of LH i.p. injections and of dorsal intra-hippocampal microinjections of Chlorpheniramine (CPA) on anxiety-related behaviors and emotional memory in male mice using elevated plus-maze (EPM). The experiment was performed in two days. On the first day (T1) 71 male Swiss Albino mice of body weight 25- 35g were pre-treated with saline (SAL) i.p. or LH (500mg/Kg) i.p. After two hours they were treated with dorsal intra-hippocampal microinjections of SAL or CPA (0.016nmol; 0.052nmol; 0.16nmol/0,1l). Five minutes after intra-hippocampal microinjections the animals were exposed to EPM for 5 minutes. Twenty four hours later the same protocol was repeated (T2). The animals were randomly assigned to 8 groups based on drug treatment: SAL/SAL (n=9), SAL/CPA1 (n=9), SAL/CPA2 (n=10), SAL/CPA3 (n=8), LH/SAL (n=10), LH/CPA1 (n=8), LH/CPA2 (n=8) and LH/CPA3 (n=9). All three doses of intra-hippocampal microinjections of CPA did not change the percentage of time spent in the open-arms (%OAT) on T1 SAL/CPA1 (46.13±4.45); SAL/CPA2 (47.59±4.89); SAL/CPA3 (44.30±6.65) when compared to control group SAL/SAL (35.84±2.77) and did not change the enclosed arm entries (EAE) SAL/CPA1 (8.56±1.06); SAL/CPA2 (9.70±1.10); SAL/CPA3 (9.38±1.25) when compared to control group SAL/SAL (10.56±1.11). Intraperitoneal injections of LH increased %OAT on T1 on LH/SAL group (59.79±4.71), when compared to control group SAL/SAL (35.84±2.77), but not EAE LH/SAL (9.20±1.78) and SAL/SAL (10.56±1.11). Animals treated with LH and CPA3 (LH/CPA3) decreased %OAT (32.25±4.81) on T1 when compared to LH/SAL (59.79±4.71) group. SAL/CPA1 animals did not decreased %OAT on T2 (T1: 46.13±4.45; T2: 39.38±6.53). The same happened to LH/CPA2 (T1: 50.10±3.99; T2: 40.97±8.22) and LH/CPA3 (T1: 32.25±4.81; T2: 32.16±6.93) groups. Thus, we conclude that: dorsal intra-hippocampal microinjection of Chlorpheniramine has no effect on anxiety-related behaviors in male mice; intraperitoneal injection of L-Histidine has an anxiolytic-like effect in male mice exposed to elevated plus-maze, that is reversed by the higher dose of Chlorpheniramine (0.16nmol/0,1l); higher doses of CPA are necessary to impair emotional memory when the levels of hippocampal histamine are elevated.
 
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Publishing Date
2012-01-10
 
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