Universidad de Buenos Aires Facultad de Farmacia y...
Nicotine is the major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, acute nicotine administration modifies locomotion, anxiety and nociception; whereas repeated nicotine administration produces behavioral responses related to its addictive properties, such as...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1121 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1121.dir/1121.PDF |
| Aporte de: |
| Sumario: | Nicotine is the major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, acute nicotine administration modifies locomotion, anxiety and nociception; whereas repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence. In our study, complementary genetic and pharmacological approaches were used to evaluate the hypothesis that GABAB receptors modulate different addictive properties of nicotine. For this purpose, acute nicotine responses (hypolocomotion, antinociception and anxietyrelated behaviors), nicotine reinforcing effects and nicotine withdrawal syndrome (somatic and motivational manifestations) were investigated in mice pretreated with baclofen (GABAB agonist) or 2-OH-saclofen (GABAB antagonist) (pharmacological approach) and in mice lacking the GABAB1 subunit (GABAB1 knockout) (genetic approach). In these animals, we also explored possible neurochemical (dopamine, noradrenaline and serotonin concentrations) and molecular (c-Fos and nicotinic receptor expression) alterations. Summarizing, we observed that behavioral, neurochemical and molecular alterations induced by nicotine addictive properties were modified by the stimulation (baclofen), the blockage (2-OH-saclofen) or the lack (GABAB1 knockout) of GABAB receptors. Concluding, these findings suggest that GABAB receptors play a role in the addictive properties of nicotine and support the hypothesis that GABAB receptor agonists could offer therapeutic advantage to treat tobacco dependence. |
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