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para-Chlorophenylalanine induces aggressive behavior by serotonin depletion in male rats and increases tryptophan hydroxylase 2 and GABAA α1 mRNA expression in the olfactory bulb.
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  • Maria Mulle Bernedo,
  • F. Campoverde,
  • Claudia Bregonzio,
  • R. Cabrera
Maria Mulle Bernedo
Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza - Argentina

Corresponding Author:belenmulle@gmail.com

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F. Campoverde
Laboratorio de Hormonas y Biología del Cáncer (IMBECU-CONICET) Mendoza - Argentina
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Claudia Bregonzio
Universidad Nacional de Cordoba Facultad de Ciencias Quimicas
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R. Cabrera
Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza - Argentina
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Decreased serotonin (5-HT) has long been linked to increased aggressive behavior. Tryptophan hydroxylase (TPH) is an enzyme involved in 5-HT synthesis and para-chlorophenylalanine (pCPA) inhibits its activity. TPH2 mRNA expression presence has been mainly described in the raphe complex rodent’s brain. 5-HT-producing neurons in the raphe project their axons to olfactory bulb, considered to be a relevant structure in rodents for establishing social interactions, including aggressive behavior. However, the relationship between olfactory bulb and aggression in a pCPA 5-HT depletion model has not been studied. Moreover, receptor subunit GABA α1 has been found in the olfactory bulb and 5-HT depletion could affect GABAA receptor expression in different brain areas. Thus, our aim was to evaluate aggressive behavior, serotonergic activity, the TPH2 and GABAA α1 mRNA expression, in the olfactory bulb, after a single pCPA (300mg/kg) or vehicle i.p. administration in male rats. Aggression was tested using a resident intruder test. Sequentially, the olfactory bulb was obtained, and neurochemical and molecular techniques were used to measure 5-HT, 5-HIAA, TPH2, and GABAA α1 mRNA expression respectively. pCPA administration increased aggressive behavior parameters, without affecting locomotion, nonsocial or social interaction. 5-HT levels were decreased after pCPA administration, as well as its turnover rate, although there were no significant changes in 5-HIAA. TPH2 mRNA expression was increased. GABAA α1 mRNA expression was increased in the olfactory bulb. Our results apport evidence to the serotonergic deficiency hypothesis of aggression and highlight olfactory bulb role as an important structure for understanding aggressive behavior neurobiological complexity.