Response of the hypothalamo-pituitary-adrenal axis to nicotine

135

The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPAaxis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed inpatients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

Section: Additional Factors Influencing the Dex-crh Testsupporting

confidence: 61%

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Künzel

Binder

Nickel

et al. 2003

135

“…We further demonstrated that nicotine indirectly induces ACTH secretion from the anterior pituitary by directly activating noradrenergic areas of the nucleus tractus solitarius (Matta et al, 1998;Zhao et al, 2007).…”

Section: Introductionmentioning

confidence: 68%

“…Nicotine is a potent stimulus for the stress-responsive HPA axis that elicits the release of the stress hormones, ACTH (Cam and Bassett, 1983b;Matta et al, 1987) and CORT (Balfour et al, 1975;Cam and Bassett, 1983a). We have previously identified a polysynaptic pathway through which nicotine acutely stimulates the HPA axis (Matta et al, 1998). Corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN), which are pivotal regulators of ACTH secretion, are not directly activated by nicotine (Matta et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress

Chen

Sharp

2007

Self Cite

We investigated the effect of chronic nicotine self-administration (SA) on hypothalamic-pituitary-adrenal (HPA) hormonal responses to acute stressors. Adult male Sprague-Dawley rats were given access to nicotine (0.03 mg/kg) for 23 h per day for 20 days. On day 1 of acquisition of nicotine SA, plasma levels of both adrenocorticotropin and corticosterone were significantly increased 15-30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were o60 pg/ml and corticosterone levels were o110 ng/ml during the hour after the first dose of nicotine. Chronic nicotine SA (20 days) significantly augmented (2-3-fold) both hormonal responses to mild foot shock stress (0.6 mA, 0.5 s per shock, 5 shocks per 5 min), but did not affect hormonal responses to moderate shock (1.2 mA, 0.5 s per shock, 5 shocks per 5 min), lipopolysaccharide or immobilization. Similar data were obtained in Lewis rats. These results provide further support for the concept that chronic nicotine SA is a stressor. In alignment with the effects of other stressors, nicotine activated the HPA axis on the first day of SA, but desensitization occurred with repeated exposure. Furthermore, chronic nicotine SA selectively cross-sensitized the HPA response to a novel stressor. These observations suggest that nicotine may selectively increase the HPA response to stressors in human smokers.

“…or i.c.v. administration and microinjection into catecholaminergic regions, and these effects are blocked by the nicotine antagonist mecamylamine (Sharp and Beyer, 1986;Matta et al, 1990Matta et al, , 1993bMatta et al, , 1998. Hypothalamic corticotropin-releasing hormone (CRH) cannot be measured in venous blood, but one index of CRH activation is the release of ACTH from the anterior pituitary, followed by an increase in cortisol in humans and corticosterone in rodents.…”

Section: Introductionmentioning

confidence: 99%

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

Mendelson

Sholar

Goletiani

et al. 2005

125

106

The acute effects of smoking a low-or high-nicotine cigarette on hypothalamic-pituitary-adrenal (HPA) hormones, subjective responses, and cardiovascular measures were studied in 20 healthy men who met American Psychiatric Association Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within four puffs (or 2 min) after cigarette smoking began, plasma nicotine levels and heart rate increased significantly (Po0.01), and peak ratings of 'high' and 'rush' on a Visual Analogue Scale were reported. Reports of 'high,' 'rush,' and 'liking' and reduction of 'craving' were significantly greater after smoking a high-nicotine cigarette than a low-nicotine cigarette (Po0.05). Peak plasma nicotine levels after high-nicotine cigarette smoking (23.972.6 ng/ml) were significantly greater than after lownicotine cigarette smoking (3.6370.59 ng/ml) (Po0.001). After smoking a low-nicotine cigarette, adrenocorticotropin hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA), and epinephrine did not change significantly from baseline. After high-nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.8875.34 pmol/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r ¼ 0.85; Po0.0001), DHEA (r ¼ 0.66; P ¼ 0.002), and epinephrine (r ¼ 0.86; Po0.0001). Cortisol and DHEA increased significantly within 20 min (Po0.05) and reached peak levels of 424748 and 21.1372.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking.