Acute effects of alprazolam and adinazolam on the concentrations of corticotropin‐releasing factor in the rat brain

Owens, Michael J.; Bissette, Garth; Nemeroff, Charles B.

doi:10.1002/syn.890040304

Cited by 87 publications

(30 citation statements)

References 78 publications

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“…This is in line with previous studies which were predominantly based on the analysis of plasma corticosterone concentrations (Bruni et al, 1980;Schürmeyer et al, 1988;Owens et al, 1989Owens et al, , 1993Kalogeras et al, 1990;Breier et al, 1991Breier et al, , 1992Schuckit et al, 1992;Torpy et al, 1993Torpy et al, , 1994Rohrer et al, 1994;Korbonits et al, 1995;Arvat et al, 1998Arvat et al, , 1999Skelton et al, 2000). However, in contrast to corticosterone, changes in plasma ACTH can be directly linked to the secretory activity of the parvocellular neurons of the PVN: AVP and CRH are secreted as releasing hormones from these neurons into the pituitary portal blood to synergistically stimulate the secretion of ACTH from the anterior pituitary (Aguilera and Rabadan-Diehl, 2000;Aguilera et al, 2001).…”

Section: Temazepam Triggers Intra-pvn Release Of Avp T Welt Et Alsupporting

confidence: 89%

Temazepam Triggers the Release of Vasopressin into the Rat Hypothalamic Paraventricular Nucleus: Novel Insight into Benzodiazepine Action on Hypothalamic–Pituitary–Adrenocortical System Activity During Stress

Welt

Engelmann

Renner

et al. 2006

Neuropsychopharmacol

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We investigated the influence of a representative classical benzodiazepine on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis activity both under basal conditions and stress. Adult male Wistar rats were intravenously administered with temazepam (0.5, 1, and 3 mg/kg body weight) and plasma concentrations of corticotropin (ACTH) and vasopressin (AVP) were measured in blood samples collected via chronically implanted jugular venous catheters. Simultaneously, the release of AVP within the hypothalamic paraventricular nucleus (PVN) was monitored via microdialysis. Plasma AVP levels remained unaffected by the different treatment conditions. Temazepam blunted the stressor exposure-induced secretion of ACTH in a dose-dependent manner. Concurrently, and also in a dose-dependent manner temazepam enhanced the intra-PVN release of AVP, known to originate from magnocellular neurons of the hypothalamic neurohypophyseal system. Furthermore, temazepam did not affect the in vitro secretion of ACTH from the adenohypophyseal cells. Taken together, the results of this study suggest that temazepam modulates the central nervous regulation of the HPA axis by altering intra-PVN AVP release. An increasingly released AVP of magnocellular origin seems to provide a negative tonus on ACTH secretion most probably via inhibiting the release of ACTH secretagogues from the median eminence into hypophyseal portal blood.

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Section: Temazepam Triggers Intra-pvn Release Of Avp T Welt Et Alsupporting

confidence: 89%

Temazepam Triggers the Release of Vasopressin into the Rat Hypothalamic Paraventricular Nucleus: Novel Insight into Benzodiazepine Action on Hypothalamic–Pituitary–Adrenocortical System Activity During Stress

Welt

Engelmann

Renner

et al. 2006

Neuropsychopharmacol

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“…Interpreted in this way, the effects of VPA would be similar to those of the benzodiazepine alprazolam. Previous results show that alprazolam alters CRF neuronal systems in accordance with the working hypothesis outlined above (Owens et al, 1989Skelton et al, 2000a), that alprazolam and VPA both increase GABAergic neurotransmission (Illig et al, 2000), and are useful in the treatment of mania (Bowden, 1998b). Therefore, one might have predicted that the effects of VPA on CRF systems would be similar to those of alprazolam.…”

Section: Discussionsupporting

confidence: 58%

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

Gilmor¹,

Skelton²,

Nemeroff³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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Corticotropin-releasing factor (CRF) plays a preeminent role in coordinating the endocrine, autonomic, and behavioral responses to stress. Dysregulation of both hypothalamic and extrahypothalamic CRF systems have been reported in patients with major depression and post-traumatic stress disorder. Moreover, effective treatment of these conditions leads to normalization of these CRF systems. Although there is virtually no data concerning alterations of CRF systems in bipolar disorder (manic depressive illness), previous work indicates that valproic acid, an anticonvulsant also effective in the treatment of acute mania, alters central CRF neuronal systems. In the current studies, we chronically administered valproic acid and lithium, two clinically effective mood stabilizers, in nonstressed rats to extend our previous findings. Chronic valproic acid administration decreased CRF mRNA expression in the paraventricular nucleus of the hypothalamus; lithium administration increased CRF mRNA expression in the central nucleus of the amygdala. Although valproic acid increased CRF 1 receptor mRNA expression in the cortex, CRF 1 receptor binding was decreased in both the basolateral amygdala and cortex, suggesting that chronic valproate treatment may in fact dampen the overall tone in this central stress pathway. Valproate treatment decreased CRF 2A mRNA expression in both the lateral septum and hypothalamus, although CRF 2A receptor binding was unchanged. Lithium administration decreased CRF 1 mRNA expression in both the amygdala and frontal cortex, but CRF 1 receptor binding also remained unchanged. These results suggest that the therapeutic actions of these mood stabilizers may, in part, result from their actions on central CRF neuronal systems. The distinct actions of each drug on CRF systems may underlie their synergistic clinical effects.

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“…Furthermore, in adult rats previously exposed to maternal separation, stress results in increased release of NE in the hypothalamus (Liu et al 1998). In a series of experiments we have found that the clinically effective anxiolytic alprazolam decreases LC CRF concentrations after acute administration, an effect that is maintained during chronic administration (Owens et al 1989(Owens et al , 1991. In view of the hypothesis that anxiety may be associated with increased activity of the LC, our findings suggest that benzodiazepines may exert at least some of their anxiolytic effects through decreasing the CRF stimulatory input to noradrenergic neurons in the LC.…”

Section: Crf and Anxietymentioning

confidence: 99%

The role of corticotropin-releasing factor in depression and anxiety disorders

Arborelius¹,

Mj²,

Plotsky³

et al. 1999

Journal of Endocrinology

1,248

688

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Corticotropin-releasing factor (CRF), a 41 amino acidcontaining peptide, appears to mediate not only the endocrine but also the autonomic and behavioral responses to stress. Stress, in particular early-life stress such as childhood abuse and neglect, has been associated with a higher prevalence rate of affective and anxiety disorders in adulthood. In the present review, we describe the evidence suggesting that CRF is hypersecreted from hypothalamic as well as from extrahypothalamic neurons in depression, resulting in hyperactivity of the hypothalamic-pituitaryadrenal (HPA) axis and elevations of cerebrospinal fluid (CSF) concentrations of CRF. This increase in CRF neuronal activity is also believed to mediate certain of the behavioral symptoms of depression involving sleep and appetite disturbances, reduced libido, and psychomotor changes. The hyperactivity of CRF neuronal systems appears to be a state marker for depression because HPA axis hyperactivity normalizes following successful antidepressant treatment. Similar biochemical and behavioral findings have been observed in adult rats and monkeys that have been subjected to early-life stress. In contrast, clinical studies have not revealed any consistent changes in CSF CRF concentrations in patients with anxiety disorders; however, preclinical findings strongly implicate a role for CRF in the pathophysiology of certain anxiety disorders, probably through its effects on central noradrenergic systems. The findings reviewed here support the hypothesis that CRF receptor antagonists may represent a novel class of antidepressants and/or anxiolytics.

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Acute effects of alprazolam and adinazolam on the concentrations of corticotropin‐releasing factor in the rat brain

Cited by 87 publications

References 78 publications

Temazepam Triggers the Release of Vasopressin into the Rat Hypothalamic Paraventricular Nucleus: Novel Insight into Benzodiazepine Action on Hypothalamic–Pituitary–Adrenocortical System Activity During Stress

Temazepam Triggers the Release of Vasopressin into the Rat Hypothalamic Paraventricular Nucleus: Novel Insight into Benzodiazepine Action on Hypothalamic–Pituitary–Adrenocortical System Activity During Stress

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

The role of corticotropin-releasing factor in depression and anxiety disorders

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