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.
Abstract
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.