Stress, Pharmacology and Behavior

The “stress” concept shows the relationship that exists between aversive stimuli that seriously disrupts the organism homeostasis and its physiological and conductual responses to harmful stimulation.

However, if this system is constantly activated, without recovery, it may begin to produce alterations such as decreased memory and concentration, lower performance, high physiological activation, tireness, insomnia, increased substance abuse, among others.

Stress is one of the most common sufferings in our society. In its natural form, stress allows us to survive and have the right adaptation in situations that can risk the individual survival, its offspring, territory or its kind; which implies that stress is necessary for a better adaptation to the environment.

The physiological changes associated with stress includes:
Disposition of energy in order to maintain the functions of the muscles and the Central Nervous System (CNS).
Increase of the attentional resources towards the stimulus stressor.
Increase of the cardiac and respiratory rates.
Redistribution of the blood flow towards muscles and CNS.
Regulation of the immune system.
Down regulation of the reproductive sexual response.
Loss of sphincter control.
Decrease of the food intake and appetite.

Stress has generally been related to over-activation of the hypothalamic pituitary-adrenal (HPA) axis. The HPA axis has been described that activates the neuroendocrine system in order to maintain a state of adaptation to stress and the maintenance of physiological regulation systems after the stressful event and thus guarantee survival.

When stress reaches such a magnitude that completely exceeds the adaptive mechanisms of the subject and does not allow him to give any adequate answers, pharmacological and physiological attention is needed.
In these cases, in addition to the symptoms mentioned, there are usually some disorders such as anxiety, depression, substance abuse and post-traumatic stress disorder (PTSD).

Around 15% of individuals who suffer a traumatic event, fail to recover and develop PTSD. It has been described that in PTSD there is persistence of the following groups of symptoms (not all of them must be present):
Those associated with the memory of the traumatic event (re-cords, intrusive thoughts, nightmares).
Hyperactivation (hyperexcitation, insomnia, agitation, irritability, impulsivity and anger).
Avoidance of the stimuli associated with the traumatic event (people, places, objects, activities), as well as an effort to avoid thoughts and feelings related to the traumatic event.
Negative alterations in thinking and mood associated with the traumatic event. There are also persistent negative beliefs about oneself, others or the world.

patients diagnosed with PTSD may also exhibit dissociative symptoms such as:
Depersonalization: Persistent or recurrent experiences of feeling separated from oneself, with feelings of unreality of the body or time that moves slowly.
Derealization: Persistent or recurrent experiences of the unreality of the environment.

It has been shown that the dysfunctional state of the HPA axis has been associated with various psychiatric and psychomotor disorders
At the level of the hypothalamus, the corticotropin-releasing factor (CRF) is released in response to stress resulting in the activation of the HPA and the consequent in-growth of cortisol.
CRF acts through the receptors coupled to G proteins CRF-1 and CRF-2. It has been described that high levels of CRF at the time of the traumatic experience facilitates the codification of traumatic memory and maintains the effects of anxiety by stimulating the CRF-1 receptors (see figure 1).

Cortisol mediates its effects through Glucocorticoid and Mineralocorticoid receptors. Although stress has primarily been related to the release of cortisol and the stimulation of its receptors, neuromodulators that have been linked to the stress response and PTSD have also been described.
Such is the case of noradrenaline (NA), dopamine (DA) and serotonin (5-Hydroxytryptamine, 5-HT). The noradrenergic and dopaminergic neurons of the brainstem change the firing rate according to the relevance of the events in the middle.
Particularly noradrenergic cells during non-stress conditions have a phasic rate of pronounced firing towards the relevant stimuli, while during stressful stimuli they present a high tonic firing change with phasic deregulation. This implies that they trigger due to relevant stimuli during the alert, but also they also trigger to irrelevant stimuli during fatigue or stress.

There is a very nice overview about the stress:

A Comprehensive Overview on Stress Neurobiology: Basic Concepts and
Clinical Implications

On this paper we can find a differentiation about the physiological vs psychological stress in the SNC. Besides is very nice historical review.

ncbi.nlm.nih.gov

A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications.

LD Godoy, MT Rossignoli, P Delfino-Pereira, N Garcia-Cairasco and EH de Lima Umeoka, Frontiers in behavioral neuroscience, 2018

Stress is recognized as an important issue in basic and clinical neuroscience research, based upon the founding historical studies by Walter Canon and Hans Selye in the past century, when the concept of stress emerged in a biological and adaptive perspective. A lot of research after that period has expanded the knowledge in the stress field. Since then, it was discovered that the response to stressful stimuli is elaborated and triggered by the, now known, stress system, which integrates a wide diversity of brain structures that, collectively, are able to detect events and interpret them as real or potential threats. However, different types of stressors engage different brain networks, requiring a fine-tuned functional neuroanatomical processing. This integration of information from the stressor itself may result in a rapid activation of the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis, the two major components involved in the stress response. The complexity of the stress response is not restricted to neuroanatomy or to SAM and HPA axes mediators, but also diverge according to timing and duration of stressor exposure, as well as its short- and/or long-term consequences. The identification of neuronal circuits of stress, as well as their interaction with mediator molecules over time is critical, not only for understanding the physiological stress responses, but also to understand their implications on mental health.

Sometimes we are used to think about stress like something bad. However the stress it could be “positive”. In these kind of stress we have the feeling about be more propositive, the arousal increase and even some cognitive processing are enhanced because the stress.

One very nice example for me is the annual meeting of the SFN, we have this sensation of butterflies in the stomach, the excitement of presenting the poster, the mixed feelings about the possible discussion with our scientific mates. However I know that that meeting is for good. Im able to differentiate this situation from another in which the danger could be for real.