Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis

Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness.

Neuroendocrine pharmacology of stress

To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20-min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH (P less than 0.01) and B (P less than 0.05) responses to stress during proestrus compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for 3 days, and injected either with oil (O'), 10 micrograms of E2 (E') 24 h before stress testing, or with E2 and 500 micrograms P 24 and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher (P less than 0.01) in the E' group compared to the EP' and O' groups. Although the peak B response was similar in all groups, the E' and EP' groups secreted more B after the termination of stress than did the O' group. Within the 20 min stress period, ACTH levels in the E' group were significantly (P less than 0.05) higher at 5, 10, and 15 min after the onset of stress, compared to the EP' and O' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (P less than 0.05 and P less than 0.01, respectively) compared to the EP' and O' group. beta-endorphin-like immunoreactive responses to restraint stress were also significantly higher in the E' group compared to the EP' (P less than 0.05) and O' (P less than 0.01) groups. In contrast to the effect seen at 24 h, ACTH responses to stress 48 h after E2 injection in the E' group were comparable to O' animals. There was no effect of E2 on ACTH clearance, whereas B clearance was enhanced in E' treated animals vs. O'-treated animals. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous. Such enhanced HPA responses to stress are limited to the early portion of proestrous, as progesterone appears to inhibit the facilitatory effects of estrogen on ACTH release during stress. Taken together, these results suggest an ovarian influence on both activational and inhibitory components of HPA activity.

/pdf/variations-in-the-hypothalamic-pituitary-adrenal-response-to-h6sq7f6kpm.pdf

Variations in the Hypothalamic-Pituitary-Adrenal Response to Stress during the Estrous Cycle in the Rat

Background: Our previous studies have suggested that combat veterans with posttraumatic stress disorder (PTSD) have alterations in hypothalamic-pituitary-adrenal axis functioning that are different from the well-documented biological changes observed in major depressive disorder and following exposure to stress. Methods: In the present study, we examined cortisol and lymphocyte glucocorticoid receptor number before and after the administration of 0.50 and 0.25 mg of dexamethasone in 14 combat veterans with PTSD, 12 combat veterans without PTSD, and 14 nonpsychiatric healthy men. All subjects were medication free at the time of testing and none met diagnostic criteria for major depression or substance dependence. Results: Combat veterans with PTSD suppressed cortisol to a greater extent than did combat veterans without PTSD and normal controls in response to both doses of dexamethasone. Differences in cortisol suppression could not be attributed to substance dependence history or differences in dexamethasone bioavailability. Combat veterans with PTSD showed a larger number of baseline glucocorticoid receptors compared with normal men. Combat veterans without PTSD also had a larger number of baseline glucocorticoid receptors compared with normal men and in fact were comparable to combat veterans with PTSD on this measure. However, only veterans with PTSD showed a decrease in lymphocyte glucocorticoid receptor number following dexamethasone administration. Conclusion: The data support the hypothesis of an enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal axis in PTSD.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=psych&articleId=497153&pdfFileName=archpsyc_52_7_010.pdf

Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder

To test the ability of the pituitary gland to secrete ACTH in response to repeated stress, 90-day-old male and female rats were subjected first to a 3-min psychological stress and then to a second identical stress 5, 10, or 15 min after the onset of the first stress. After decapitation 5, 10, 15, 20, 25, or 35 min after the onset of the second stress, plasma ACTH concentration was determined by bioassay, and plasma corticosterone was measured by a fluorometric method. Although the rate of increase in plasma corticosterone levels after the first stress was about 1.4 μg/100 ml-min in males and 2.1 μg/100 ml-min in females, 5-15 min after the onset of the first stress, no rapid inhibition of the second stress response appeared. Gradual hypersecretion of ACTH occurred in males after exposure to the second stress, and the resultant peak increment in plasma ACTH concentration was 2–3 times greater than the one observed in once-stressed rats. In females, a rapid and significant increase in plasma ACTH concentrat...

Temporal changes in plasma adrenocorticotropin concentration after repeated neurotropic stress in male and female rats.

Reports of the response of the hypothalamo-hypophysial-adrenal axis to stress have involved measurement of the levels of corticosterone and/or adrenocorticotrophin (ACTH) in the plasma of intact and adrenalectomized rats. It is known that the size and kinetics of the adrenal response are dependent on the nature of the stress and the sex of the rat (Kitay, 1961; Lescoat, Jego, Beraud & Maniey, 1970). From work on the effect of stress on plasma ACTH (Lutz, Koch & Miahle, 1969; Cook, Kendall, Greer, & Kramer 1973; Usategui, Oliver, Vaudry, Lombardi, Rosenberg & Mourre, 1976), the nature of the stress and the parameters of the response appear to be related and Barrett (1960) reported that the release of ACTH in response to stress is greater in female than in male rats. This work describes the kinetics and size of the release of ACTH in male and female rats subjected to mild neurotropic stress. Male and female 90-day-old Sherman rats, born in the laboratory, were caged in groups of six under conditions of controlled lighting (lights on 07.00-19.00 h) and temperature (23 CC). The animals were then caged singly for 14 h before being subjected to stress: they

G. Beraud

Papers

Temporal changes in plasma adrenocorticotropin concentration after repeated neurotropic stress in male and female rats.

Dynamic changes in plasma adrenocorticotrophin after neurotropic stress in male and female rats.