Naloxone‐induced Acth Release in Man Is Inhibited by Clonidine

Jackson, R. V.; Grice, Jeffrey E.; Jackson, Andrew; Gi, Hockings

doi:10.1111/j.1440-1681.1990.tb01302.x

Cited by 35 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the monkey, we have previously demonstrated that inhibitory effects of CRH and of vasopressin on pulsatile LH release occur through the activation of endogenous opiate peptides since both effects are prevented by naloxone infusion [20,40]. That the cortisol increase following LPS persists in the presence of naloxone may not be surprising, since naloxone itself is known to stimulate the HPA axis in several species [41][42][43].…”

Section: Discussionmentioning

confidence: 98%

Inhibitory Effects of Endotoxin on LH Secretion in the Ovariectomized Monkey Are Prevented by Naloxone but Not by an Interleukin-1 Receptor Antagonist

Xiao¹,

Xia‐Zhang²,

Ferin³

1999

Neuroimmunomodulation

View full text Add to dashboard Cite

Endotoxin (lipopolysaccharides, LPS), the pathogenic moiety of gram-negative bacteria, is a well-known trigger for the central release of cytokines. The objective of this study is to evaluate the effects of systemic endotoxin administration on LH and cortisol secretion in a non-human primate model and to investigate whether these endocrine effects are mediated by centrally released interleukin-1 (IL-1) using the receptor antagonist to IL-1 (IL-1ra). An additional objective is to investigate whether endogenous opioid peptides mediate these endocrine effects of LPS, using the opiate antagonist naloxone. The experiments were performed in long-term-ovariectomized rhesus monkeys. Blood samples for hormone determination were obtained at 15-min intervals for a period of 8 h, which included a 3-hour baseline period. Since the effective central dose of IL-1ra in the monkey was unknown, in the first experiment we tested the potency of several doses of this antagonist in preventing the effects of centrally administered IL-1α, a cytokine which is known to inhibit LH and stimulate cortisol release. Rhesus monkeys received a 30-min intracerebroventricular infusion of IL-1α (4.2 μg/30 min) alone or together with various doses of IL-1ra (30–180 μg/h i.c.v.). IL-1ra infusion was initiated 1 h before IL-1 and extended over the experimental period. As previously reported, IL-1α induced a significant inhibition of LH, to 36.5 ± 3.3% (mean ± SE) by 5 h as a percentage from the 3-hour baseline. This inhibitory effect was reversed by cotreatment with the 180 µg/h dose of IL-1ra (to 82.5 ± 3.8% by 5 h; NS vs. saline) but not with the lower doses. IL-1 stimulated cortisol release to 165.9 ± 7.7%, but this increase was prevented by IL-1ra (66.6 ± 8.9%; p < 0.05 vs. IL-1, NS vs. saline). In the second experiment, LPS (50 μg) was administered intravenously, alone or in combination with intracerebroventricular IL-1ra infusion. LPS induced a significant decrease in LH secretion (to 57.1 ± 5.2%). These effects were not reversed by intracerebroventricular administration of IL-1ra (52.5 ± 9.6%). Cortisol secretion increased in response to LPS, but this stimulatory effect was not affected by IL-1ra (178.3 ± 13.4 vs. 166.9 ± 5.7%). There were no effects of IL-1ra alone. In experiment 3, we investigated whether the opiate antagonist naloxone reverses the endocrine effects of endotoxin. Both LPS (50 μg) and naloxone (5-mg bolus + 5 mg/h) were infused intravenously. Naloxone was effective in preventing the inhibitory effect of LPS on LH (to 124.6 ± 22.1%, NS vs. saline) but not the increase in cortisol (to 166.7 ± 16.7%; p < 0.05 vs. saline, NS vs. LPS). Naloxone alone has no significant effect on LH or cortisol secretion. These data demonstrate that, in the ovariectomized monkey, a systemic inflammatory/immune- like stress challenge acutely inhibits tonic LH secretion while concomitantly stimulating cortisol release. Although endotoxin is known to affect central cytokine release, these endocrine effects do not require a mediatory role of central IL-...

show abstract

Section: Discussionmentioning

confidence: 98%

Inhibitory Effects of Endotoxin on LH Secretion in the Ovariectomized Monkey Are Prevented by Naloxone but Not by an Interleukin-1 Receptor Antagonist

Xiao¹,

Xia‐Zhang²,

Ferin³

1999

Neuroimmunomodulation

View full text Add to dashboard Cite

show abstract

“…Decreases in cortisol levels during placebo administration could be a consequence of pain relief or part of the endogenous opioid modulation of the hypothalamicpituitary-adrenal axis. Hypothalamic corticotrophin-releasing hormone neurons receive direct inhibitory input from b-endorphin producing neurons in the arcuate nucleus, but also regulate corticotrophin-releasing hormone neurons indirectly through noradrenergic mechanisms (Jackson et al, 1990). Naloxone, a non-selective opioid receptor antagonist, induces increases in adrenocorticotropic hormone and cortisol levels, an effect thought to be mediated through the blockade of b-endorphin and enkephalinergic input to corticotrophin-releasing hormone neurons (Bujdoso et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

Peciña

Azhar

Love

et al. 2012

Neuropsychopharmacol

166

107

View full text Add to dashboard Cite

Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of m-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses. Molecular imaging showed that subjects scoring above the median in a composite of those trait measures also presented greater placebo-induced activation of m-opioid neurotransmission in the subgenual and dorsal anterior cingulate cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala and periaqueductal gray (PAG). Endogenous opioid release in the dorsal ACC and PAG was positively correlated with placebo-induced reductions in pain ratings. Significant reductions in cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings, m-opioid system activation in the dorsal ACC and PAG, and as a trend, negatively with NEO Angry Hostility scores. Our results show that personality traits explain a substantial proportion of the variance in placebo analgesic responses and are further associated with activations in endogenous opioid neurotransmission, and as a trend cortisol plasma levels. This initial data, if replicated in larger sample, suggest that simple trait measures easily deployable in the field could be utilized to reduce variability in clinical trials, but may also point to measures of individual resiliency in the face of aversive stimuli such as persistent pain and potentially other stressors.

show abstract

“…The hypothalamic CRH neurons receive direct inhibitory input from b-endorphin-producing neurons located in the arcuate nucleus. In addition, b-endorphinproducing neurons inhibit norepinephrine neurons, which provide direct stimulatory input to hypothalamic CRH neurons (Jackson et al, 1990). One could posit that compared with individuals expressing only the A allele, persons expressing the G allele (and hence a higher-affinity MOR) have higher inhibitory opioidergic tone directed at CRH neurons.…”

Section: Discussionmentioning

confidence: 99%

The Mu-Opioid Receptor Polymorphism A118G Predicts Cortisol Responses to Naloxone and Stress

Chong

Oswald

Yang

et al. 2005

Neuropsychopharmacol

142

103

View full text Add to dashboard Cite

A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase b-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamicpituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n ¼ 74) and/or the modified Trier Social Stress Test (TSST) (n ¼ 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (Po0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P ¼ 0.046), but a lower cortisol response to the TSST (P ¼ 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.

show abstract

Naloxone‐induced Acth Release in Man Is Inhibited by Clonidine

Cited by 35 publications

References 25 publications

Inhibitory Effects of Endotoxin on LH Secretion in the Ovariectomized Monkey Are Prevented by Naloxone but Not by an Interleukin-1 Receptor Antagonist

Inhibitory Effects of Endotoxin on LH Secretion in the Ovariectomized Monkey Are Prevented by Naloxone but Not by an Interleukin-1 Receptor Antagonist

Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

The Mu-Opioid Receptor Polymorphism A118G Predicts Cortisol Responses to Naloxone and Stress

Contact Info

Product

Resources

About