These experiments investigated the effect of either systemic opiate blockade by naloxone (5 mg/kg) or intracerebroventricular CRF (250 pmol), or the two treatments combined, on physiological and endocrine responses of male rats to two types of stress: restraint by itself (representing a psychological stress), and restraint combined with a tail clip (representing an additional mild physical nociceptive stress). Rats were restrained in a plastic container for 15 min, with or without a tail clip. Heart rate, body temperature, and serum corticosterone were measured. The first experiment showed that restraint induced marked tachycardia, maximal at 5 min, and declining thereafter. There was also a pronounced hypothermia, maximal at 10 min, and serum corticosterone was elevated 10 min after the end of the period of restraint. The presence of a tail clip increased the cardioaccelerator response, but had no effect on hypothermia. Naloxone had no effect on heart rate during restraint or on postrestraint corticosterone, but accentuated hypothermia. The effects of naloxone occurred independently of the presence of a tail clip. A subsidiary experiment showed that rats transferred to an unfamiliar cage showed a marked hyperthermic response, as described by others. The second experiment showed that CRF (250 pmol ICV) did not modify the tachycardiac response to restraint, but reduced hypothermia. This also occurred irrespective of the presence of a tail clip. The third experiment investigated the interaction between naloxone and CRF, and showed that the ameliorative effects of ICV CRF on restraint-induced hypothermia were prevented by systemic naloxone, but that neither tachycardia nor corticosterone responses were altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Diurnal variations in endocrine and psychological responses to 0.2 mg/kg naloxone administration in patients with major depressive disorder and matched controls.

BACKGROUND: There is evidence that the endogenous opioid system (EOS) is involved in the modulation of mood and neuroendocrine function. Furthermore, the possible involvement of the EOS in major depression has been postulated, although a clear role has not been established. METHODS: The affective and endocrine responses to naloxone administration in seven female depressives and in seven matched controls and their diurnal variations were investigated. Subjects had an i.v. bolus of either 0.2 mg/kg naloxone or saline at two time points (09:00 or 18:00 h) and for 2 days in a single-blind, cross-over design. RESULTS: The basal cortisol plasma levels, both in the morning and in the afternoon, showed higher values (P<0.05) in the depressives. There was a naloxone-induced increase in the adrenocorticotrophic hormone (ACTH), cortisol, and luteinizing hormone (LH) plasma levels, plus a subjective dysphoric effect in both groups. The depressives showed a greater dysphoric effect both in the morning and afternoon (P<0.05), and a blunted cortisol response in the afternoon (P<0.05). There were no differences between groups or time of day in the ACTH or LH responses. LIMITATIONS: The sample size was small, but by studying each patient as their own control, plus a matched control for every patient, softens this effect. Finding patients with a major depressive episode free of medication is difficult, and this aspect contributes to the size of the sample. CONCLUSIONS: These results suggest that opioid mechanisms may be involved in the HPA axis changes and possibly in mood changes found in depression. The discrepancy between increased sensitivity in depression to mood changes and decreased change in cortisol may indicate a ceiling effect for the latter.

Adrenocorticotropic Hormone↗

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Neurosteroids, brain damage, and mental illness.

The steroidal environment of the brain has marked consequences for both its structure and function. Social or physical stress has deleterious results on hippocampal function. This can be replicated by raising corticoids, which are also highly responsive to stress. Corticosterone, the major glucocorticoid in the rat, induces neuronal death in primary hippocampal cultures. Elevated corticoids also induce mood changes, and these are well known to be associated with stress, particularly chronic stress such as social adversity accentuated by intercurrent aversive life events. DHEA, a second adrenal steroid, has a very different developmental history, increasing rapidly during childhood, reaching a peak in youth, and declining thereafter in both blood and CSF. DHEA, in contrast to corticoids, has brain protective actions. It reduces the neurotoxic actions of glutamate analogues (such as NMDA) as well as those of corticoids. Evidence from several sources suggests that DHEA can act as an antiglucocorticoid. DHEA levels are reduced in major depressive disorders in both adolescents and adults, and a raised cortisol/DHEA ratio (together with intercurrent life events) predicts delayed recovery. DHEA may have a role in the treatment of depression. Together, these findings suggest that altered steroidal environment, whether induced by stress or aging, can have appreciable results on the cellular structure of the brain as well as on its function, although links between the two sets of findings are still tentative.

Adrenal Cortex Hormones↗

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Endangerment of the brain by glucocorticoids: experimental and clinical evidence.

In this paper, we review studies suggesting that elevated glucocorticoids increase the susceptibility of the brain to adverse events. The events themselves can be varied, and their effects on the brain can also differ. The common feature is that glucocorticoids may modulate the likelihood (risk) of damage or malfunction following adversity. In the first part of our paper, we describe experimental studies on the brain's cellular response to neurotoxins that support this thesis; in the second, we survey clinical evidence that indicate that glucocorticoids may endanger the brain's response to adverse social events. We suggest that there may be common features in the experimental and clinical findings. To begin, however, we draw attention to some of the properties of the hypothalamic-pituitary-adrenal (HPA) axis that seem relevant to our discussion.

Animals↗

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Fluoxetine improves emotional incontinence.

Emotional incontinence is a behavioural syndrome characterized by involuntary weeping, grimacing, and/or laughter. We investigated the efficacy of fluoxetine in 13 patients with emotional incontinence. All 13 patients demonstrated dramatic improvement in emotional lability within 3 to 14 days.

Adult↗

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