Introduction
Aggressiveness is considered a social behavior since it requires at
least two subjects, and it can be either defensive or offensive. Among
primates, humans and rodents there are similarities in aggressive
neurobiology (Takahashi et al., 2011; Niederkofler et al., 2016). The
aggressive spectrum displayed depends on the specie, the sex, the
stimuli, and the contextual contingency (Niederkofler et al., 2016;
Takahashi et al., 2011; Takahashi & Miczek, 2014). According to the
qualitative and quantitative features aggressiveness in rodents, could
be considered as adaptive or maladaptive (Muroy et al., 2016). In their
natural environment, rodents are strongly aggressive to defend their
food resources, reproductive possibilities and territory (Takahashi et
al., 2012). The resident vs. intruder test (RVI) is the most validated
paradigm to measure this kind of interaction (Takahashi & Miczek,
2014).
Serotonin (5-HT) plays an important role in social behavior. Among
others, modulates several behaviors, such as copula, postnatal care,
adolescent social playing, maternal and territorial aggressiveness
(Berger et al., 2009; Buhot et al., 2000; Mittal et al., 2017; Strüder
& Weicker, 2001; Takahashi et al., 2012). Many systems are involved in
aggressive behavior (Chamero et al., 2011; Carrillo et al., 2009; Duke
at al., 2013) Although, serotonergic deficiency hypothesis establish an
inverse relationship between the serotonergic system activity and
aggressive behavior (Cervantes & Delville, 2009; Kravitz & Huber,
2003; Miczek et al., 2004; Mongillo et al., 2014; Takahashi et al.,
2011; Niederkofler et al., 2016; van Erp & Miczek; 2000). In rodent
models, there are several ways to generate aggressiveness by decreasing
5-HT: neurotoxicity, olfactory bulbectomy, social isolation, and
pharmacological depletion (Hritcu et al., 2007; Jéquier et al., 1967;
Koe & Weissman, 1966; Vergnes et al., 1988). Para-chlorophenylalanine
(pCPA) is an irreversible TPH enzyme inhibitor. An intraperitoneal pCPA
administration causes an acute decrease within the central serotonergic
system (Jáquier, 1967; Hritcu et al., 2007) and it has been used to
generate aggression models (Jáquier, 1967; Keleta et al., 2007; Kubala
et al., 2008).
5-HT producing neurons in the raphe complex project their axons to the
cortex, amygdala, hippocampus, basal ganglia, thalamus, hypothalamus,
and olfactory bulb (OB) (Lesch & Waider, 2012; Mazerolle et al., 2016).
OB is an important serotonergic innervated structure (Huang et al.,
2017; McLean & Shipley, 1987; Steinfeld et al., 2015) and the main
sensory information used by rodents to start social interactions, such
as aggressive behavior, is olfaction (Guillot & Chapouthier, 1996).
Moreover, Lucki (1998) showed that 5-HT synthesis inhibition in OB rats
caused increased aggressiveness, whereas enhancement transmission
suppressed aggressive behavior. First sensory center that processes odor
information is the OB, a structure that has been considered when
studying territorial aggression (Bester-Meredith et al., 2022).
Nonetheless, the relationship between OB and aggression in a pCPA 5-HT
depletion model has not been studied.
5-HT is synthesized through the tryptophan hydroxylase (TPH) enzyme
(Khan & Thomas, 2004). TPH gene has two isoforms (Walther et al.,
2003), while the TPH1 isoform is mostly expressed outside the
blood-brain barrier, the TPH2 isoform is expressed in the cerebral
tissue and its mRNA expression has so far been mostly described in raphe
complex neurons (Malek et al., 2005; Patel et al., 2004; Pelosi et al.,
2015; Walther et al., 2003). A human brain post-mortem study, showed
TPH2 expression in the cortex, thalamus, hypothalamus, hippocampus,
amygdala, cerebellum, and raphe nuclei (Zill et al., 2007). A study
using catfishes (Raghuveer et al.; 2011) reported TPH2 mRNA expression
in OB. Furthermore, Patel et at., (2004) showed that TPH2 mRNA
expression in rat brain revealed a very weak signal in the OB.
Principal neurons and local interneurons in OB have GABAA receptors with
different subunit components (Panzanelli, 2005). Particularly, the
presence of GABAA receptor subunit α1 mRNA in the OB has been described
(Zhang et al., 1991) and is the most common GABAA α subunit in adult
rodent neurons (Bosman et al., 2002). In addition, it has been reported
that 5-HT depletion could affect GABAA receptor expression in different
brain areas (Si et al., 2022; Wang et al., 2020).
Our aim was to evaluate aggressive behavior, serotonergic activity in
the OB, TPH2, and GABAA α1 mRNA expression in the OB, after a single
pCPA i.p administration in male rats.