γ-Aminobutyric acid neural signaling in the lateroanterior hypothalamus modulates aggressive behavior in adolescent anabolic/androgenic steroid-treated hamsters

Abstract

Male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated and mature forms of offensive aggression correlated with increased γ-aminobutyric acid (GABA) afferent development as well as decreased GABAA receptors in the latero-anterior hypothalamus (LAH) – an area of convergence for developmental and neuroplastic changes that underlie offensive aggressive behaviors in hamsters. This study investigated whether microinfusion of a GABAA receptor agonist (muscimol; 0.01 – 1.0 pM) or antagonist (bicuculline; 0.04 – 4.0 pM) directly into the LAH modulate adolescent AAS-induced offensive aggression. Activation of LAH GABAA receptors enhanced adolescent AAS-induced offensive aggression, beginning at the 0.1pM dose, when compared with AAS-treated animals injected with saline into the LAH. Importantly, GABAA receptor agonism within the LAH significantly increased the frequency of belly/rear attacks, while simultaneously decreasing the frequency of frontal attacks. These data identify a neuroanatomical locus where GABAA receptor activation functions to enhance aggression in adolescent AAS-treated animals, while also promoting the display of mature forms of aggression and suppressing juvenile play behaviors.

Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus

“…Interestingly, blockade of GABA receptor signaling increases bursting activity in neurons within various brain regions (Urbain, Rentéro, Gervasoni, Renaud, & Chouvet, 2002), and together with our results, this report suggests that increased GABA signaling can tonically silence bursting neuron activity in a given brain region. Along with previous behavioral pharmacology studies from our lab showing that the GABA system, in part, modulates AAS-induced aggressive behavior (Morrison, Ricci, & Melloni, 2014b), our electrophysiological data may help characterize novel characteristics of GABA circuits and identify unique drug targets that can be used to reverse maladaptive AAS alterations to behavior.…”

Dopamine D2 receptors act upstream of AVP in the latero-anterior hypothalamus to modulate adolescent anabolic/androgenic steroid-induced aggression in Syrian hamsters.

“…In our animal model of adolescent AAS-induced offensive aggression, the majority of AAS-treated adolescents target their offensive responses to the lateral flank/rump regions of intruders (Morrison et al, 2014; Ricci, Morrison, & Melloni, 2013; Schwartzer & Melloni, 2010a, 2010b), that is, a hallmark characteristic of the adult aggressive phenotype (Taravosh-Lahn & Delville, 2004; Wommack & Delville, 2003). Thus AAS-treated animals display the adult form of offensive aggression in the absence of social experience, indicating that adolescent exposure to AAS may circumvent the learning of mature fighting behavior.…”

“…Following the microinjection regimen, animals were placed back in their home cages for 5–10 min, and then tested for offensive aggression using the resident-intruder paradigm, that is, a well-characterized and ethologically valid model of offensive aggression in Syrian hamsters (Floody & Pfaff, 1974; Lerwill & Makings, 1971). Briefly, a novel intruder of similar size and weight was introduced into the home cage of the experimental animal (resident) and the resident was scored for general (composite, bites, attack latency) and targeted (frontal attacks, lateral attacks, and flank bites), aggressive responses as previously described (Grimes et al, 2003; Morrison, Ricci, & Melloni, 2014; Ricci et al, 2006). An attack was scored each time the resident animal would pursue and then either lunge toward and/or confine the intruder by upright and sideways threat; each generally followed by a direct attempt to bite the intruder’s face/head (frontal attack) or lateral or dorsal flank/rump (lateral attack) target area(s).…”

Neuroendocrine mechanisms of aggression in rodents.

“…GABAergic neurons can inhibit excitatory signals in the BNST, POA, and hypothalamus, areas known for their role in aggression (Herman et al, 2004). In male golden hamsters, activation of latero-anterior hypothalamus (LAH) GABA A receptors increased adolescent androgenic-anabolic steroid (AAS)-induced aggression by suppressing juvenile play behaviors in favor of more mature forms of aggression such as belly and rear attacks (Morrison et al, 2014), again showing how the internal hormonal environment can influence this transition from play fighting to adult aggression. AAS also increased expression of the rate-limiting enzyme for GABA in the AH, VLH, and MeA (Grimes et al, 2003).…”