Dopamine in Extreme Environments: Dopamine Control, Part Two.
The Hypothalamic-Pituitary-Adrenal axis or HPA axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis.
During childhood, abnormal development of the HPA axis can result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery.
These ingredients together create the perfect storm to affect an individual later on in life. These changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood and in some cases develop during childhood or alter biomarkers, which act as early warning systems, permanently.
The primary function of the HPA axis is to regulate your stress response.
(2-Minute Neuroscience: HPA Axis - YouTube, n.d.)
Activation of the HPA axis results in widespread hormonal, neurochemical and physiological alterations. Inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the brain’s Basal Ganglia (responsible for motor control, executive functions, behavior, and emotions). Dysfunction of neurotransmitters and their receptors can lead to dopamine-relevant corticostriatal reward circuitry.
Findings have included inflammation-associated reductions in ventral striatal responses to reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine. The ventral striatum is the striatal region most closely associated with reward.
Dopamine response exhibits increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. There has been mounting interest regarding the role of cytokines in behavioral alterations and the development and progression of neuropsychiatric disorders. This means that inflammatory response derived from stress-response drives both brain and behavior changes, among many other types of physiological dysfunction.
Cytokines from peripheral immune cells can access the Central Nervous System (CNS) by several mechanisms including:
1) Passage through leaky regions in the blood-brain-barrier such as the circumventricular organs.
2) Activation of endothelial cells and perivascular macrophages in the cerebral vasculature to produce local inflammatory mediators such as cytokines, chemokines, prostaglandins, and nitric oxide.
3) Carrier-mediated transport of cytokines across the blood-brain-barrier.
4) Local activation of peripheral nerve afferents which then relay cytokine signals to relevant brain regions, including the nucleus of the solitary tract and hypothalamus.
5) Recruitment of activated immune cells such as monocytes/macrophages and T cells from the periphery to the brain, where these cells can, in turn, produce cytokines.
“Under physiologic conditions, cytokines such as Tumor Necrosis Factor or TNF-alpha and IL-1 have been shown to be involved in a number of essential brain processes such as synaptic remodeling, neurogenesis, and long-term potentiation. However, in excess, inflammatory cytokines can act in the brain to affect monoamine neurotransmitter systems and behavior, and recent evidence indicates that dopamine function in the basal ganglia may be a primary target in this regard. The basal ganglia are key subcortical structures that regulate motivation and motor activity, and dopamine plays an essential modulatory role in basal ganglia function. The effect of inflammatory cytokines on basal ganglia dopamine may be especially relevant to depression and fatigue as well as psychomotor disturbances and the development of neurodegenerative disorders” (Felger & Miller, 2012).
Chronic inflammation and exposure to inflammatory cytokines lead to changes in the basal ganglia and dopamine function which result in very specific behaviors to include anhedonia (inability to feel pleasure), fatigue, and psychomotor slowing. The reduction of neural responses to hedonic reward (pleasure), decreased dopamine metabolites in CSF or cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been reported.
Peripheral inflammatory cytokines or activated immune cells can dramatically influence local inflammatory networks and drive neuroinflammation (inflammatory response of brain and spinal cord) by activating local production of cytokines and inflammatory signaling pathways.
Inflammatory cytokines and their receptors are expressed in the brain at low levels during non-pathological states and are found to be fairly ubiquitous, yet this cytokine network in the brain can be rapidly mobilized in response to inflammatory stimuli. Examples of inflammatory stimuli could be what you consume; your environment; a run-in with the wrong person; a memory. These are all examples of inflammatory stimulus which would trigger an inflammatory response leading to an uptick in inflammatory cytokines released into the brain and into the body, more specifically the central nervous system.
Cytokines in the brain are produced primarily by microglia, but can also be produced by astrocytes and to some extent by neurons and oligodendrocytes. Endothelial cells and perivascular macrophages respond to circulating cytokines to induce expression of prostaglandin-producing enzymes cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PGES).
Following acute inflammatory stimulus, increased central nervous system inflammation signal a protection response to the brain, and acute changes in neurotransmitter metabolism, including increases in monoamines such as serotonin and norepinephrine in the hypothalamus, can contribute to the induction of fever, activation of the HPA axis, and transition from an anabolic to a catabolic state.
Changes in monoamine metabolism promote behavioral alterations including reduced locomotor activity and anhedonia that allow for shunting of energy and metabolic resources to combat infection and/or facilitate wound healing. Cytokine signals from the periphery alert the central nervous system of immune insult in order to prepare and protect an organism during times of sickness and injury.
Under conditions of chronic inflammation such as during chronic medical illnesses, extreme stress, or operating in an extreme environment, central nervous system inflammation can exert profound and protracted changes in neurotransmitter systems, neurotrophic factors, and neuronal integrity that can have negative and even detrimental outcomes on behavior.
Dopamine Control provided by the directives of psychological field kits intervene in the inflammatory response, which results in the return to homeostasis. Personalized psychological field kits reduce HPA axis activation or mitigate dysfunction by allowing the body to return to baseline even at times of extreme stress, for example during high-stress mission operations or crises within an extreme environment.
“Dopamine” by Italian Artisi, Maria Elena Buemi (Dopamine (Molecola Della Creatività) Painting by Maria Elena Buemi | Saatchi Art, n.d.).
Dopamine in Extreme Environments: Dopamine Control, Part Three, coming soon.
References
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Dopamine (molecola della Creatività) Painting by maria elena buemi | Saatchi Art. (n.d.). Retrieved January 13, 2022, from https://www.saatchiart.com/art/Painting-Dopamine-molecola-della-Creativit/683742/3362178/view
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About the author:
Melanie began attending Harvard in 2020 to complete a Graduate Certificate in Human Behavior with a specialization in Neuropsychology. Boling’s research has examined extreme environments and how they can have a potential negative impact on humans operating in the extreme environment. During her time at Harvard, she has built a mental wellness tool called a psychological field kit. Implementing these tools will allow an individual to thrive in an extreme environment while mitigating negative variables such as abnormal human behavior which can play a role in team degradation.