Cortisol Melatonin Growth hormone Testosterone in men Autonomic balance

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1 1 Hormones, Neurochemistry, & Behaviour 7 - Homeostasis + Stress Cortisol Melatonin Growth hormone Testosterone in men Autonomic balance Some major circadian rhythms Suprachiasmatic Nucleus (SCN) of the Hypothalamus - mammalian biological clock - bi-lateral lesions disrupt circadian organization of behaviour and hormones like cortisol and testosterone - controlled by input from retina and by melatonin - slices of SCN continue to show circadian rhythm in vitro - many melatonin receptors - actions of estradiol and testosterone GENERAL ADAPTATION SYNDROME: Acute Phases Acute Stress (Emergency Reaction) - Sympathetic NS - Adrenal Catecholamine Release - Central Catecholamine Turnover Rebound - Parasympathetic NS - Slow sympathetic deactivation - Central ACh GENERAL ADAPTATION SYNDROME: Chronic Phases Resistance (Chronic Stress) - HPA activation - Enhanced Acute Stress Response - Enhanced Central Monoamine Activity Exhaustion - Idiosyncratic - Psychopathology, Physical Disease, Death

2 HPA Axis Prolonged HPA activation CRF (CRH) from hypothalamus stimulates release of ACTH and ß-endorphin from anterior pituitary ACTH stimulates adrenal cortex to produce and release corticosteroids and has direct effects on DA + NE in brain via ventricles Brain Chemistry Responds to Chronic Stress Steroid receptors hypothalamus, hippocampus, amygdala, septum Some steroids act as MAO inhibitors, thereby increasing 5-HT, NE, + DA activity ACTH can increase central NE + DA activity However, exhaustion can be associated with monoamine depletions Chronic extreme cortisol levels can alter hippocampal structure CRF Stimulates ACTH and thus adrenal cortex Alters neurotransmitters and behaviour via central actions Can activate central 5-HT activity Facilitates locomotor activity, fleeing behaviour, swimming Decreases ingestive and reproductive behaviour Effects are highly conserved across vertebrates 2 Stress and Female Reproduction Acute inhibitors of female sexual response: Stressors Catecholamine activation Intense sympathetic NS arousal Corticosteroids (some species) Chronic inhibitors: Chronic stress / HPA activation -> disrupted, anovulatory cycles Stress can block intrauterine implantation of fertilized ova Spontaneous abortion, fetal growth inhibition can result from post-implantation stressors Chronic adrenocortical excess Central monoamine depletions Weight gain or loss Appetite disturbance Sleep disturbance Loss of libido Lethargy, motor retardation Hyper- or hypo-sensitive emergency reaction Psychophysiological responses Growth Suppression Death Phase of Exhaustion

3 3 Dexamethasone Suppression Test Dexamethasone a synthetic glucocorticoid blocking ACTH via hypothalamus + pituitary Administration to healthy people can suppress glucocorticoids Absence of suppression suggests: - ectopic ACTH (tumours) - adrenal tumours (neoplasms can autonomously secrete cortisol) Corticosteroids Bind selectively in limbic system: hypothalamus, amygdala, hippocampus, septum In moderate levels, cortisol can inhibit MAO (monoamine oxidase), which breaks down 5HT, DA, and NE, promoting positive affect However, chronically high levels of cortisol are correlated with psychological depression, which is also related to monoamine depletion Chronic Stress + Hippocampus Long-term uncopable stress (exhaustion) can cause cell loss in the hippocampus Chronic excessive cortisol implicated May be mitigated by sugar in diet However, hippocampus is one of few areas in brain where new cells can be formed Hunger + Thirst Insulin: peptide - 51 amino acids vertebrates and invertebrates only hormone to lower blood glucose facilitates glucose uptake by cells Glucagon: peptide - 29 amino acids stimulates liver: glycogen to glucose Pancreatic Hormones Blood Glucose Decreased blood glucose leads to hunger Intracellular glucose is important (insulin) Hunger/feeding correlate with low levels Liver receptors are critical (hepatic portal vein) Liver information reaches hypothalamus via the vagus nerve

4 4 Neuropeptide Y (NPY) Widely distributed in nervous system Co-released from NE neurons Active in hypothalamus during hunger (paraventricular and arcuate nuclei at base of 3 rd ventricle) NPY is reduced in well-fed state Food deprivation leads to increased NPY In rats, injection of NPY into hypothalamus leads to ravenous and frantic eating Ghrelin secreted by epithelial cells lining empty stomach rises in blood during fasting signals hunger and stimulates feeding Leptin 167 amino-acid peptide secreted by adipose decreases feeding increases metabolism receptors concentrated in arcuate hypothalamus inhibits NPY secreting neurons higher levels at night CCK (cholecystokinin) released when food reaches the small intestine acts on stomach to stimulate vagus nerve injecting CCK reduces feeding and food seeking behaviour Bombesin small protein in GI tract and nervous system injections reduce appetite unlike CCK, this action is not affected by cutting vagus Extracellular Thirst Blood volume decreases Blood pressure decreases Triggered by blood loss, perspiration, diarrhea, heavy menstrual bleeding Requires replacement of sodium, etc. as well as water Baroreceptors in kidneys -> renin (kidneys) -> angiotensin (blood) -> aldosterone (adrenal cortices) -> kidneys save Na+ Angiotensin causes vasoconstriction & may stimulate thirst via actions in brain Angiotensin2 may stimulate vasopressin (ADH) release

5 5 Cellular Thirst Induced by excess salt consumption or severe thirst Increased extracellular Na+ Osmotic force draws H 2 0 from cells Osmoreceptors around hypothalamus - regions by 3 rd ventricle) The Ventricular System Concentrated saline applied around 3 rd ventricle induces drinking Distilled water to this area causes drinking cessation Sodium appetite Involves angiotensin and aldosterone Injection of angiotensin into brain increases NaCl intake This is enhanced by aldosterone administration