Involvement of GABAB receptors in biochemical alterations induced by anxiety-related responses to nicotine in mice: Genetic and pharmacological approaches

NEUROPHARMACOLOGY

卷:81

Article

Varani, Andres P.¹  Pedron, Valeria T.¹  Bettler, Bernhard²  Balerio, Graciela N.^1,3 

[1] Consejo Nacl Invest Cient & Tecn, Inst Invest Farmacol, RA-1033 Buenos Aires, DF, Argentina

[2] Univ Basel, Pharmazentrum, Inst Physiol, Dept Biomed, CH-4056 Basel, Switzerland

[3] Univ Buenos Aires, Fac Farm & Bioquim, Catedra Farmacol, RA-1113 Buenos Aires, DF, Argentina

关键词: Nicotine;    GABA(B) receptor;    2-OH-saclofen;    Anxiety;    Catecholamine;    c-Fos;   

DOI  :  10.1016/j.neuropharm.2014.01.030

来源: Elsevier

【 摘 要 】

Previous studies from our laboratory showed that anxiety-related responses induced by nicotine (NIC), measured by the elevated plus maze, were abolished by 2-OH-saclofen (GABA(B) receptor antagonist) (1 mg/kg; ip) or the lack of GABA(B) receptors (GABA(B1) knockout mice). Based on these behavioral data, the aims of the present study were: 1) to evaluate the possible neurochemical changes (dopamine, DA, serotonin, 5-HT, 3,4-dihydroxyphenylacetic acid, DOPAC, 5-hydroxyindoleacetic acid, 5-HIAA and noradrenaline, NA) and the c-Fos expression induced by the anxiolytic (0.05 mg/kg) or anxiogenic (0.8 mg/kg) doses of NIC in the dorsal raphe (DRN) and lateral septal (LSN) nucleus; 2) to study the possible involvement of GABAB receptors on the neurochemical alterations and c-Fos expression induced by NIC (0.05 and 0.8 mg/kg), using both pharmacological (2-OH-saclofen) and genetic (mice GABABi knockout) approaches. The results revealed that in wild-type mice, NIC (0.05 mg/kg) increased the concentration of 5-HT and 5-HIAA (p < 0.05) in the DRN, and NIC (0.8 mg/kg) increased the levels of 5-HT (p < 0.01) and NA (p < 0.05) in the LSN. Additionally, 2-OH-saclofen pretreatment (1 mg/kg, ip) or the lack of GABAB receptors abolished these neurochemical changes induced by NIC (p < 0.01, p < 0.05, respectively). On the other hand, NIC 0.05 and 0.8 mg/kg increased (p < 0.01) the c-Fos expression in the DRN and LSN respectively, in wild-type mice. In addition, 2-OH-saclofen pretreatment (1 mg/kg, ip) or the lack of GABAB receptors prevented the c-Fos alterations induced by NIC (p < 0.01). In summary, both approaches show that GABAB receptors would participate in the modulation of anxiolytic- and anxiogenic-like responses induced by NIC, suggesting the potential therapeutic target of these receptors for the tobacco addiction treatment. (C) 2014 Elsevier Ltd. All rights reserved.

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