Para-chlorophenyl alanine induces aggressive behavior by serotonin depletion in male rats and increases tryptophan hydroxylase two and gabaa α1 mrna expression in the olfactory bulb

Abstract

Decreased serotonin (5-HT) has long been linked to increased aggressive behavior. Tryptophan Hydroxylase (TPH) is an enzyme involved in the 5-HT synthesis, and para- chlorophenyl alanine (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 the olfactory bulb, considered a relevant structure in rodents for establishing social interactions, including aggressive behavior. However, the relationship between the olfactory bulb and aggression in a pCPA 5-HT depletion model has not been studied.Moreover, receptor subunit GABAα1 has been found in the olfactory bulb, and 5-HT depletion could affect GABAA receptor expression in different brain areas. Thus, we aimed to evaluate aggressive behavior, serotonergic activity, and the TPH2 and GABAAα1 mRNAexpression, 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. The olfactory bulb was obtained, and neurochemical and molecular techniques were used to measure 5-HT, 5-HIAA, TPH2, and GABAAα1 mRNA expression, respectively. pCPA administration increased aggressive behavior parameters without affecting locomotion, non-social or social interaction. 5-HT levels were decreased after pCPA administration and its turnover rate, although there were no significant changes in 5-HIAA. TPH2 mRNA expression was increased. GABAAα1 mRNA expression wasincreased in the olfactory bulb. Our results apport evidence to the serotonergic deficiency hypothesis of aggression and highlight the olfactory bulb’s Role as an essential structure for understanding aggressive behavior neurobiological complexity.