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

Abstract

In pubertal male Syrian hamsters, exposure to anabolic/androgenic steroids (AAS) during adolescence facilitates a high level of offensive aggression modulated by the enhanced development and activity of the vasopressin (AVP) and dopamine (DA) neural systems within the latero-anterior hypothalamus (LAH), i.e., a brain region implicated in the control of aggression. The present studies provide a detailed report of the pharmacologic interactions between AVP and DA D2 receptor signaling within the LAH in the control of adolescent AAS-induced offensive aggression. Male Syrian hamsters were treated with AAS throughout adolescence and tested for aggression after local infusion of the DA D2 receptor antagonist eticlopride (ETIC) alone, or in combination with AVP in the LAH in an effort to determine the influence of DA D2 receptors relative to AVP-receptor mediated aggression mechanisms. As previously shown, ETIC infusion into the LAH suppressed adolescent AAS-induced aggressive responding; however, the AAS-induced aggressive phenotype was rescued by the co-infusion of AVP into the LAH. These behavioral data indicate that interactions between AVP and DA neural systems within the LAH modulate the control of aggression following adolescent exposure to AAS and that DA D2 receptor signaling functions upstream of AVP in the LAH to control this behavioral response.

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

“…This model is supported by data that show that AAS increases: LAH AVP release, the density of both DA cells and D2 receptors in the LAH, and the density of LAH GABA neurons (Melloni & Ricci, 2010; Schwartzer et al, 2009). Behavioral data align with this model by showing that exogenous AVP in the LAH rescues AAS-induced aggression that is inhibited by D2 antagonists (Morrison et al, 2015b). In support of this model, it is likely that we recorded fewer ETIC sensitive cells within the LAH of AAS animals because we only recorded spontaneous action potentials, and thus although there exists more D2 containing neurons in AAS animals than vehicle controls, the majority of these cells are (presumably) tonically silenced GABA neurons.…”

“…Our previous behavioral pharmacological experiments exploit these changes by showing that D2 antagonist injection into the LAH inhibits AAS-induced aggressive behavior (Morrison et al, 2015b; Schwartzer & Melloni, 2010a, 2010b). A putative neural model circuit (Model 1 in Figure 10) that explains ETIC’s effect on aggression assumes that AAS-increased DA neurons within the AH tonically inhibit GABA neurons (that synapse onto AVP terminals) via activation of inhibitory D2 receptors (Schwartzer et al, 2009).…”

“…In a series of studies, we have shown that adolescent AAS exposure alters several neurotransmitter systems implicated in the control of aggression within the latero-anterior subregion of the hypothalamus (LAH) that include the vasopressin (AVP) (Carrillo et al, 2011a; Grimes, Ricci, & Melloni, 2006; Grimes et al, 2007; Harrison et al, 2000; Melloni & Ricci, 2010), serotonin (5HT) (Grimes & Melloni, 2002, 2005; Ricci, Rasakham, Grimes, & Melloni, 2006), and dopamine (DA) (Morrison, Ricci, & Melloni, 2015b; Schwartzer, Ricci, & Melloni, 2009) neural systems.…”

“…Anabolic androgenic steroids enhance the presence of D2 receptors within the LAH (Ricci et al, 2009; Schwartzer et al, 2009), and local injection of Eticlopride (i.e., a D2-receptor antagonist) dose-dependently inhibits AAS-induced aggression (Schwartzer & Melloni, 2010a). Recently, we showed that co-injection of AVP with Eticlopride into the LAH rescues the AAS-aggressive phenotype from the inhibitory effects of D2 antagonism, suggesting that DA mechanisms that regulate aggressive behavior in the LAH lie upstream of AVP-sensitive cells (Morrison et al, 2015b). …”