Factors modifying the effect of diazepam on plasma corticosterone levels in rats

Pohorecky, Larissa A.; Cotler, S.; Carbone, John J.; Roberts, Patricia

doi:10.1016/0024-3205(88)90367-0

Cited by 23 publications

(7 citation statements)

References 13 publications

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“…A direct or indirect effect of diazepam on steroidogenesis through its receptors in the adrenal cortex or the anterior pituitary gland is unlikely because the dose we used was reported to be ineffective. 31 However, our finding of higher corticosterone plasma levels in control LH rats is in keeping with the elevated urinary corticosterone levels found in 20-week-old LH rats maintained under unstressed physiological conditions. 32,33 High plasma corticosterone levels in LH rats raise the question of the impact of glucocorticoids in the physiopathology of hypertension in this strain.…”

Section: Morphological and Functional Alterations Of The Adrenal Glansupporting

confidence: 67%

Hypersensitivity of the Adrenal Cortex to Trophic and Secretory Effects of Angiotensin II in Lyon Genetically-Hypertensive Rats

et al. 2004

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In Lyon hypertensive (LH) rats, a model of low-renin genetic hypertension, we investigated adrenal sensitivity to angiotensin II in terms of angiotensin II receptor (AT1 and AT2 receptors) regulation, morphological changes, and aldosterone and corticosterone secretion. Twelve-week-old LH rats, compared with normotensive LN and LL rats, were either untreated or treated for 4 weeks with AT1 receptor antagonist irbesartan (50 mg/kg/d), angiotensin-converting enzyme inhibitor perindopril (3 mg/kg/d), or perindopril (3 mg/kg/d) plus angiotensin II infusion (200 ng/kg/min). At 16 weeks, untreated LH rats had high systolic blood pressure (P<0.05), low aldosterone (P<0.05), and increased corticosterone (P<0.05) plasma levels. AT1-receptor binding density in the zona glomerulosa was similar in the three strains. In LH rats, angiotensin II infusion increased the relative adrenal weight from 10.5+/-0.3 to 16.7+/-0.7 mg/100g (P<0.05), whereas this change was very modest in normotensive rats. Zona glomerulosa enlarged and plasma aldosterone increased after angiotensin II infusion in the 3 strains, but more markedly in LH versus normotensive rats (2.4- versus 1.3- and 1.6-fold, respectively; 20- versus 10-fold in normotensive rats, P<0.05). Surprisingly, after angiotensin II infusion, despite the absence of angiotensin II receptors in the three strains, the zona fasciculata-reticularis enlarged 1.5-fold and plasma corticosterone increased 1.7-fold only in LH rats (P<0.05), suggesting an indirect control of this compartment by angiotensin II. The hypertrophy and hypersecretory activity of both zona glomerulosa and zona fasciculata-reticularis in LH rats in response to angiotensin II point to the adrenal cortex as a pivotal tissue in the pathophysiology of hypertension in LH rats.

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Section: Morphological and Functional Alterations Of The Adrenal Glansupporting

confidence: 67%

Hypersensitivity of the Adrenal Cortex to Trophic and Secretory Effects of Angiotensin II in Lyon Genetically-Hypertensive Rats

et al. 2004

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“…could be solely attributed to its actions on PBRs. Administration of diazepam increases plasma level of corticosterone with plasma peak after 90 minute of injection, via acting on PBRs on adrenal glands [23, 24]. It has been shown that endogenous glucocorticoids are important factors for acinar cell survival which protects acinar cells by decreasing their sensitivity to the cell death during cerulein induced acute pancreatitis [13].…”

Section: Discussionmentioning

confidence: 99%

Effect of Diazepam on Severity of Acute Pancreatitis: Possible Involvement of Peripheral Benzodiazepine Receptors

Abed

Minaiyan

Safaei

et al. 2013

ISRN Gastroenterology

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Acute pancreatitis is a lethal inflammatory condition of pancreas with high mortality rate. There is a pressing need for research to explore active agents and novel mechanisms involving in the treatment of pancreatitis. Clinical studies have shown after the initial acinar cell injury plasma levels of pro-inflammatory cytokines are elevated in patients with acute pancreatitis and the degree of cytokine elevation correlates with disease severity. Diazepam may decrease interleukin release from macrophages, suppress neutrophil activities, and exhibit anti-inflammatory effects. So it is expected that in vivo pretreatment of acute pancreatitis with different doses of diazepam can attenuate its severity. Thus, we evaluated the effects of diazepam, intraperitoneally (5, 10, and 20 mg/kg i.p.), intracerebroventricularly (ICV 10 μg), and concurrently with flumazenil (1 mg/kg) on cerulein-induced acute pancreatitis in mice. Interestingly, the pretreatment with diazepam (5 mg/kg i.p.) reduced significantly the inflammatory response of acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, myeloperoxidase activity, pancreatic TNF-alpha, and pathological alteration compared to control group. Diazepam i.c.v. was ineffective, suggesting that central benzodiazepine receptors have no significant role in this property. These results demonstrate that pretreatment with diazepam exhibits anti-inflammatory property in cerulein-induced acute pancreatitis possibly through peripheral benzodiazepine receptors.

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“…The present study confirms these findings by showing improved accuracy and limb coordination associated with diazepam treatment. The response to diazepam treatment followed an inverted U‐shape function with an optimum effect on skilled reaching success at 2.5 mg. An acute dose of 2.5 mg diazepam also reduced CORT levels, which is in accordance with data presented by Pohorecky et al . (1988).…”

Section: Discussionmentioning

confidence: 99%

“…In turn, treatment with anxiolytic drugs, including ethanol (Metz et al ., 2003) and benzodiazepines (Lepicard et al ., 2003), can significantly improve skilled motor performance. These effects might be related to changes in stress hormone levels because treatment with benzodiazepines affects circulating CORT levels (Pohorecky et al ., 1988; Kalman et al ., 1997).…”

Section: Introductionmentioning

confidence: 99%

Modulation of motor function by stress: a novel concept of the effects of stress and corticosterone on behavior

Metz

Jadavji

Smith

2005

Eur J of Neuroscience

127

108

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Stress and stress hormones affect a variety of behaviors and cognitive abilities. The influences of stress and glucocorticoids on motor function, however, have not been characterized although the presence of glucocorticoid receptors in the motor system has been documented. Here we demonstrate that stress and the stress hormone corticosterone influence motor system function in rats. Groups of adult female Long-Evans rats underwent either a daily stress-inducing procedure (immobilization or swimming in cold water) or oral corticosterone treatment. While these treatments continued, animals were tested in skilled reaching and skilled walking tasks for a period of 2 weeks. Both acute (day 1) and chronic (day 14) stress and corticosterone treatment reduced skilled movement accuracy in reaching and walking and increased performance speed. Furthermore, both chronic stress and chronic corticosterone treatment altered skilled movement patterns in the reaching task. These findings indicate that stress modulates motor system function and that these effects are partially mediated by glucocorticoids. To examine whether stress-induced changes might also derive from enhanced emotionality, rats were treated with the benzodiazepine diazepam. Based on an inverted U-shaped dose-response relationship, a moderate dose of diazepam significantly improved reaching success while at the same time reducing corticosterone levels. Thus, stress-associated emotional responses such as anxiety might account for diminished movement accuracy. These results suggest that stress affects the motor system both directly via hormonal changes and indirectly via changes in emotionality. These findings are discussed with respect to the role of stress in motor system function and movement disorders.

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Factors modifying the effect of diazepam on plasma corticosterone levels in rats

Cited by 23 publications

References 13 publications

Hypersensitivity of the Adrenal Cortex to Trophic and Secretory Effects of Angiotensin II in Lyon Genetically-Hypertensive Rats

Hypersensitivity of the Adrenal Cortex to Trophic and Secretory Effects of Angiotensin II in Lyon Genetically-Hypertensive Rats

Effect of Diazepam on Severity of Acute Pancreatitis: Possible Involvement of Peripheral Benzodiazepine Receptors

Modulation of motor function by stress: a novel concept of the effects of stress and corticosterone on behavior

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