Brain and Behaviour (4): Stress, Anxiety and Aggression

Stress

A physiological reaction to perceived threats that can be adaptive or harmful.

What does the Sympathetic Adrenal Medullary (SAM) system do during stress?

Activates the adrenal medulla via the hypothalamus and sympathetic nervous system to release epinephrine and norepinephrine → "Fight or Flight” response

What happens in the Hypothalamic Pituitary Adrenal (HPA) axis?

Hypothalamus releases CRH → Pituitary releases ACTH → Adrenal cortex releases glucocorticoids, which regulates long-term stress response.

How can stress be neurotoxic?

Chronic glucocorticoid exposure can damage hippocampal neurons via excessive glutamate and Ca2+ influx.

Evidence of Stress-induced Neurotoxicity

Diamond et al. (1999): Found Increased glucocorticoids and impaired hippocampal function/spatial memory when rats were exposed to cat stimuli.

PTSD

A lasting psychological disorder triggered by trauma cues, especially involving interpersonal violence. (conditioned response)

What are risk factors for PTSD?

• Genetics

• Hippocampus size: Smaller hippocampus → Reduced ability to detect threatening vs safe contexts

What brain changes occur as a result of PTSD?

• Reduced hippocampus size

• Increased amygdala activity

• Reduced PFC activity.

How does therapy affect PTSD brains?

• Decreases amygdala activity

• Increases PFC and hippocampal size & activity.

What is the principle behind exposure therapy for PTSD?

Extinction learning: reduces response to cues by repeated safe exposure. The brain learns that cues do not represent threat

Anxiety

Apprehensive uneasiness or nervousness over an impeding or anticipated ill. It becomes a disorder when feelings are inappropriate for the circumstances.

Panic Disorder

Episode attacks of acute anxiety involving hyperventilation, faintness, etc

What brain regions are involved in anxiety disorders?

• Amygdala (increased activity)

• Prefrontal cortex (decreased activity)

• Anterior cingulate cortex

What types of drug are used to treat anxiety?

• GABAergic drugs (e.g., benzodiazepines)

• Neurosteroids

• SSRIs (e.g. fluvoxamine)

• DCS

What is the action of benzodiazepines (GABAergic drug)?

Agonists at GABA receptors, increasing Cl- influx and hyperpolarizing neurons.

How does XBD173 work in anxiety?

Enhances neurosteroid synthesis, boosting GABA receptor activity without sedation or withdrawal.

What brain regions control aggressive behaviour?

• Brainstem

• PAG

• Hypothalamus

• Amygdala

What serotonin-related findings are linked to aggression?

• Low serotonin correlates with higher aggression

• SSRIs reduce aggression.

What type of drug can be used to treat PTSD, Anxiety and Aggression?

SSRIs

How can aggression be rewarding?

• Individuals can exhibit “appetitive aggression” - motivated by intrinsic reward →

• Aggression can activate the dopamine system

How has Conditioned Place Preference (CPP) shown aggression to be rewarding?

Mice prefer and repeatedly choose locations where they can have an aggressive encounter with an intruder mouse (even in their absence).

Which brain areas are associated with reward?

• The Mesolimbic Pathway (including the nucleus accumbens (NAc)

• Ventral Tagmental Area (VTA)

What biochemical is used to detect activated neurons?

Fos (protein)

Evidence of the reward system in aggression

Golden et al. (2019): Aggression activated neurons (containing Fos) in the Nucleus Accumbens (NAc)