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.
[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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Acute gastrointestinal events (mostly manifested by nausea, vomiting, or loss of appetite) are class effects of all cholinesterase inhibitors, which are prescribed for the treatment of Alzheimer's disease. The underlying mechanism, however, has been unclear. Because corticotropin-releasing hormone is related to appetite control, we focused on the activation of the hypothalamo-pituitary-adrenal system and food intake following the administration of the cholinesterase inhibitor, donepezil, in rats. We monitored the plasma concentrations of adrenocorticotropic hormone, c-Fos, in the paraventricular nucleus, and intakes of rat chow for 3 h after the first administration of donepezil, and 2 weeks later, after daily administration of donepezil. The intragastric administration of 3 mg/kg of donepezil significantly increased the plasma adrenocorticotropic hormone levels and c-Fos expression in the paraventricular nucleus, and decreased the food intake on the first day. The increase in adrenocorticotropic hormone and loss of appetite after oral administration of the drug were attenuated after daily administration for 2 weeks.
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