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Title: Diurnal variations in the psychological and endocrine responses to naloxone administration in man
Author: del Campo, Martin
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1992
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5 studies investigated the circadian variation (i.e. during each 24 hours period) in endogenous opioid system (EOS) regulation of mood and neuroendocrine function in 40 male normal controls, 8 female psychiatric patients with depressive syndromes and 8 matched controls (i.e. matched with the depressed patients for age and sex). Psychological, endocrine and cardiovascular responses to the opioid antagonist naloxone were measured at different times of the day. Each subject was used as his/her own control by having successive administrations of naloxone and saline solution, or vice-versa. Naloxone induced expected rises in adrenocorticotropin hormone (ACTH), cortisol, and lutenizing hormone (LH) (p< 0.01), and a dysphoric effect in all doses used in normal controls and patients with depressive syndromes (p< 0.05). These effects are consistent with previous reports, suggesting that the EOS has an inhibitory role in the modulation of the hypothalamic - pituitary- adrenal axis and a modulatory role in mood function. These effects showed significant relationships between dose of naloxone and (i) the degree of the cortisol and mood responses (p< 0.05), and (ii) diurnal variation (p< 0.05), i.e. effects were more marked in the afternoon tests compared with tests in the morning. The dysphoric effect which was associated with naloxone in both depressed patients and normal controls was more marked in depressed patients (p< 0.05), suggesting an increased sensitivity to naloxone-induced mood effects in this group of depressed patients. Depressed patients showed a reduced cortisol response to naloxone administration (p< 0.05) in the afternoon and significantly higher baseline values compared to controls (p< 0.01), whereas there was no significant difference in ACTH response to naloxone administration. These findings suggest that there may be a limit (i.e. a ceiling) to the naloxone-induced rise in cortisol and that the EOS has a diurnal variation in activity. A 12-hour continuous (10 mg bolus + 7 mg/hr) regime of naloxone administration significantly (p = 0.05) impaired cognitive function in normal controls as shown by increased choice reaction time, reduced ability to recall the order of letters and numbers, and reduced accuracy of spatial orientation. These findings are consistent with previous reports and suggest that endogenous opioids may be involved in cognitive functions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available