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

Abstract

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

Anabolic androgenic steroid abuse in the United Kingdom: An update

“…The adolescent brain, still in development, is more susceptible to negative effects of anabolic androgenic steroid use (Lumia & Mcginnis, ; for review, see Clark & Henderson, ), which can change cell types and activity patterns within the hypothalamus (Morrison, Sikes, & Melloni, ). The adolescent brain is primed for steroid‐dependent changes; thus, changes may occur which would not be seen in adult users (Henderson et al, ).…”

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

“…Other drugs that can induce AB are antihistamines, statins, and anabolic steroids [154–156]. In children, second-generation antihistamines can produce aggression, agitation, and hyperactivity [154].…”

“…It is not surprising that AB is a common adverse reaction to anabolic-androgenic steroids (AAS) [133, 156, 157]. Studies have shown that AAS not only increase AB temporarily, but also may lead to psychiatric long-term consequences as their use in or close to puberty may induce permanent changes in the developing brain [133, 156, 157]. AAS has been shown to modify the expression of cerebral androgen, GABA A , and DA receptors, as well as affect the 5-HT system and the levels of neuroactive substances, e.g., vasopressin, substance P, and stress hormones [133].…”

Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

“…In addition to these neurotransmitter effects, vasopressin is known to be a key modulator of androgen effects by directing androgen action in the hypothalamus to coordinate outward aggression or threat avoidance/anxiety (Morrison et al, 2016a ). Synthetic androgens affect the firing of these vasopressin neurons via indirect effects on serotonergic and dopaminergic pathways within this circuit (Morrison et al, 2016b ). Prefrontal—amygdala signaling neurons are also affected via suppression of serotonergic tone (Ambar and Chiavegatto, 2009 ), suggesting a primary impact on prefrontal—limbic control of behavior in response to salient emotional or rewarding stimuli.…”