Publisher Summary This chapter discusses the regulation of function in the adrenocortical system. There are three major characteristics that describe most changes in activity of the system: (1) the circadian rhythm in basal activity, (2) stress-induced activation, and (3) corticosteroid feedback regulation. The first two may occur on very different timescales, and it is probably a consequence of the differing temporal demands that the third, corticosteroid feedback inhibition, is exerted by a variety of mechanisms over time. At any time of the day, the adrenocortical system can be activated by application of stressors. These include alteration of the value of a regulated variable or may be invoked by subjecting an animal to sudden disturbances of its environment, for example, noise, flashing lights, handling, strange environment, mild heat or cold. The adrenocortical system may be activated by traumatic stimuli or by psychological stimuli—in man, examinations, or mental arithmetic, or medical school admissions exams; in rats, unexpected decreases in food rewards.

Regulation of ACTH secretion: variations on a theme of B.

1: Biological Response to Stress: Implications for Animal Welfare, G P Moberg, University of California, USA 2: Some Issues in the Interpretation of Behavioural Responses to Stress, J Rushen, Dairy and Swine Research and Development Centre, Agriculture and Agri-food Canada, Canada 3: Neoroendocrine Responses to Stress, R L Matteri, J A Carroll and C J Dyer, University of Missouri, USA 4: The Metabolic Consequences of Stress: Targets for Stress and Priority of Nutrient Use, T H Elsasser et al., USDA, Agricultural Research Service, USA 5: Immune System Response to Stress, F Blecha, Kansas State University, USA 6: Hands-on and Hands-off Measurement of Stress, C J Cook et al., Horticultural and Food Research Institute of New Zealand, New Zealand 7: Accumulation and Long-Term Effects of Stress in Fish, C B Schreck, Oregon State University, USA 8: Chronic Intermittent Stress: A Model for the Study of Long Term Stressors, J Ladewig, The Royal Veterinary and Agricultural University, Denmark 9: Quantifying Some Responses to Pain as a Stressor, D J Mellor, Massey University, New Zealand, C J Cook and K J Stafford, Horticultural and Food Research Institute of New Zealand, New Zealand 10: Multiple Factors Controlling Behaviour: Implications for Stress and Welfare, F Toates, The Open University, Milton Keynes, UK 11: Chronic Social Stress: Studies in Nonhuman Primates, S P Mendoza, J P Capitanio and W A Mason, University of California, USA 12: Consequences of Stress During Development, D C Lay Jr., Iowa State University, USA 13: Early Developmental Influences of Experience on Behaviour, Temperament, and Stress, W A Mason, University of California, USA 14: Genetic Selection to Reduce Stress in Animals, T G Pottinger, NERC Institute of Freshwater Ecology, Windermere Laboratory, Cumbria, UK 15: Human-Animal Interactions and Animal Stress, P H Hemsworth and J L Barnett, Agriculture Victoria, Australia 16: Alleviating Stress in Zoo Animals with Environmental Enrichment, K Carlstead, National Zoological Park, Washington, USA and D Shepherdson, Oregon Zoo, USA 17: Understanding the Role of Stress in Animal Welfare: Practical Considerations, T L Wolfle, formerly of the Institute for Laboratory Animal Research, National Research Council, National Academy of Sciences, USA

The biology of animal stress: basic principles and implications for animal welfare.

Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence

Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.

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The Effects of Opioids and Opioid Analogs on Animal and Human Endocrine Systems

The involvement of dopamine neurotransmission in behavioral responses to novelty is suggested by reports that reward is related to increased dopamine activity, that dopamine modulates exploratory behavior in animals, and that Parkinson9s disease patients report diminished responses to novelty Some studies have reported that polymorphisms of the human dopamine D4 receptor (D4R) gene are associated with personality inventory measures of the trait called “novelty-seeking” To explore a potential role for the D4R in behavioral responses to novelty, we evaluated D4R-knock-out (D4R−/−) and wild-type (D4R+/+) mice in three approach–avoidance paradigms: the open field, emergence, and novel object tests These three paradigms differ in the degree to which they elicit approach, or exploratory behavior, and avoidance, or anxiety-related behavior Thus, we used these three tests to determine whether the D4R primarily influences the exploratory or the anxious component of responses to approach–avoidance conflicts D4R−/− mice were significantly less behaviorally responsive to novelty than D4R+/+ mice in all three tests The largest phenotypic differences were observed in the novel object test, which maximizes approach behavior, and the smallest phenotypic differences were found in the open field test, which maximizes avoidance behavior Hence, D4R−/− mice exhibit reductions in behavioral responses to novelty, reflecting a decrease in novelty-related exploration

https://www.jneurosci.org/content/jneuro/19/21/9550.full.pdf

Dopamine D4 Receptor-Knock-Out Mice Exhibit Reduced Exploration of Novel Stimuli

Plasma corticosterone concentrations sensitively reflect levels of stimulus intensity in the rat.

Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0-5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.

Inhibition of the Pituitary-Adrenal Response to Stress during Deprivation-Induced Feeding

https://ntrs.nasa.gov/api/citations/19810006092/downloads/19810006092.pdf

Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

1. The relationship between adrenalcortical hormones, adrenocorticotrophic hormone (ACTH), and pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 °C.

2. Bilateral adrenalectomy increased the sensitivity to pain, but adrenal demedullation had no effect.

3. Pain sensitivity was inversely related to the circadian changes in circulating corticosterone and was greater at 7 a.m. than at 7 p.m. However, the same variation in pain sensitivity existed if the adrenals were removed, suggesting that the increase in pain sensitivity after adrenalectomy was not related directly to the levels of corticosteriods.

4. The time course of the increase in pain sensitivity after adrenalectomy paralleled that of the changes in circulating ACTH. Adrenalectomy markedly increased pain sensitivity at 9 and 18 days following surgery when circulating ACTH levels were markedly elevated and corticosterone was absent, but not at 3 days following adrenalectomy when ACTH levels were lower and corticosterone was absent.

5. Hypophysectomy decreased the sensitivity to pain.

6. The results indicate that ACTH can alter pain sensitivity and that the effect of corticosteroids on the sensitivity to pain is an indirect one by virtue of their negative feed-back action on the hypothalamic-pituitary system.

John P. Heybach

Papers

Plasma corticosterone concentrations sensitively reflect levels of stimulus intensity in the rat.

Inhibition of the Pituitary-Adrenal Response to Stress during Deprivation-Induced Feeding

Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

The effect of pituitary-adrenal function in the modulation of pain sensitivity in the rat.

Dietary quinine reduces body weight and food intake independent of aversive taste