Sequence of pituitary-adrenal cortical hormone responses to low-dose physostigmine administration in young adult women and men.
ABSTRACT We previously demonstrated greater HPA axis activation in adult men compared to adult women following low-dose administration of the anticholinesterase inhibitor, physostigmine (PHYSO). Because blood sampling was done infrequently following PHYSO, the rise times of AVP, ACTH1-39, and cortisol could not be determined. In the present study, we determined the sequence of hormone increases by frequent blood sampling following PHYSO. Twelve adult women and 12 adult men underwent three test sessions 5-7 days apart: PHYSO, saline control, and repeat PHYSO. As in the earlier study, PHYSO produced no side effects in half the subjects and mild side effects in the other half, with no significant female-male differences. None of the hormone responses was significantly correlated with the presence or absence of side effects. In both women and men, the AVP increase preceded the ACTH1-39 increase, which in turn preceded the cortisol increase. The AVP and ACTH AUCs were significantly positively correlated in both women and men, supporting AVP as an acute stimulus to ACTH secretion. Also as in the earlier study, the AVP response to PHYSO was more than twice as great in men as in women, but the difference was not statistically significant. We therefore analyzed the results of both studies combined (N=26 women and 26 men). The men had a significantly greater AVP response and a trend toward a greater ACTH1-39 response compared to the women. These findings further support the concept of sexual diergism (functional sex difference) in the influence of CNS cholinergic systems on HPA hormone secretion.
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Article: Drugs and HPA axis[Show abstract] [Hide abstract]
ABSTRACT: This paper outlines the interferences of the most widely used drugs with hypothalamo-pituitary-adrenal function and the related laboratory parameters, with the purpose of providing practical help to clinicians during testing for hypo- or hypercortisolemic states.Pituitary 05/2008; 11(2):219-29. DOI:10.1007/s11102-008-0114-6 · 2.22 Impact Factor
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ABSTRACT: Nalbuphine, a mixed mu-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed mu-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamic-pituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV) + cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18–35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine + nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine's effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine's positive subjective effects, and that the subjective and cardiovascular effects of cocaine + nalbuphine in combination were not additive.Pharmacology Biochemistry and Behavior 02/2009; DOI:10.1016/j.pbb.2008.09.007 · 2.82 Impact Factor
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ABSTRACT: It is well known that physostigmine (PHY) and other anticholinesterase (anti-ChE) agents induce hypothermia in rodents but little is known about the mechanism of action. Because arginine vasopressin (AVP) has been found to be an endogenous antipyretic molecule in the CNS, we determined if PHY-induced hypothermia is linked to the endogenous release of AVP. Core temperature and motor activity were monitored by telemetry in rats maintained at an ambient temperature of 25 degrees C. Tail skin temperature was also measured at 30min intervals to estimate nonevaporative heat loss. The central cholinergic antagonist, scopolamine (1mg/kg; ip) and an AVP V(1) receptor antagonist (30microg/kg; ip) were administered during the period of PHY (200microg/kg; sc) induced hypothermia at 10am. Plasma AVP concentration and plasma cholinesterase (ChE) activity were measured at 50min after administration of PHY or scopolamine, respectively. PHY led to a rapid reduction in core temperature concomitant with a marked increase in heat loss from the tail. The hypothermic response of PHY was blocked by the AVP V(1) receptor antagonist. Administration of scopolamine also reversed the hypothermic responses and led to marked elevations in motor activity. Plasma AVP levels increased markedly at 50min after PHY and plasma ChE activity was significantly reduced by PHY. The results clearly demonstrate that PHY-induced hypothermia was blocked by the AVP V(1) antagonist and associated with elevations in plasma AVP, suggesting a novel role for AVP in the mechanism of action of anti-ChE agents.Life sciences 10/2009; 85(15-16):586-91. DOI:10.1016/j.lfs.2009.08.011 · 2.30 Impact Factor