Plasma corticosterone and brain catecholamines in stress: Effect of psychotropic drugs

Keim, Kevin L.; Sigg, E.B.

doi:10.1016/0091-3057(77)90162-9

Cited by 114 publications

(25 citation statements)

References 21 publications

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“…stimulates the activ ity of the HHA axis, are in agreement with the results of other authors [4,12,13,18]. When diazepam (10 mg/kg) was given in combination with picrotoxin and bicuculline, the GABA-A receptor blocking agents and diazepam anta gonist [see 3).…”

Section: Discussionsupporting

confidence: 81%

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Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

1986

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Picrotoxin (1 mg/kg, i.p.) and a high dose of diazepam (10 mg/kg, i.p.) increased the concentration of plasma corticosterone in nonstressed rats. This effect of diazepam was unaffected by picrotoxin and bicuculline (GABA-A receptor blockers), atropine (a muscarinic receptor blocker), apomorphine (a dopamine receptor agonist), haloperidol (a dopamine receptor blocker) and yohimbine (an alpha-2-adrenergic receptor blocker); but was blocked by clonidine (an alpha-2-receptor agonist) and this effect of clonidine was reversed by yohimbine. Diazepam was unable to elevate plasma corticosterone levels in rats pretreated with dexamethasone. Clonidine and the GABA-B receptor agonist, baclofen, failed to affect the picrotoxin-induced rise of plasma corticosterone, but this rise was abolished by a low dose of diazepam (1 mg/kg). The results suggest that the diazepam-induced enhancement of ACTH release, presumably mediated by blockade of alpha-2-adrenergic receptors, is responsible for the observed increase of plasma corticosterone level in rats. On the other hand, the elevation of plasma corticosterone induced by picrotoxin appears to be mediated by GABA-A receptors.

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Section: Discussionsupporting

confidence: 81%

“…High doses of diazepam enhance [16,17,20], while low doses decrease plasma corticosterone levels in nonstressed rats [20,21]. The ability of a high dose of diaze pam to increase plasma corticosterone level in rats has also been reported by other authors [4,12,13,18]. Diazepam is know-n to facilitate the action of GABA at GABA-A recep tors [24, see also 3].…”

mentioning

confidence: 85%

Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

1986

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“…Since forskolin-stimulated CRH activity was inhibited by clozapine, chlorpromazine, haloperidol, and thioridazine, it can be expected that these drugs should also inhibit stress-stimulated CRH synthesis. In fact, haloperidolFwhich decreased forskolin-induced CRH activityFhas been found to inhibit stress-induced rise in plasma corticosterone in rats (Keim and Sigg, 1977). Figure 6 The effect of chlorpromazine and clozapine applied at the indicated concentrations for 5 days on PKA (basal and cAMP-stimulated) and phosphatidylserine-stimulated PKC activity in differentiated Neuro-2A cells.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic Drugs Inhibit the Human Corticotropin-Releasing-Hormone Gene Promoter Activity in Neuro-2A Cells—an Involvement of Protein Kinases

Basta‐Kaim

Budziszewska

Jaworska-Feil

et al. 2005

Neuropsychopharmacol

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Antipsychotic drugs can regulate transcription of some genes, including those involved in regulation of hypothalamic-pituitary-adrenal (HPA) axis, whose activity is frequently disturbed in schizophrenic patients. However, molecular mechanism of antipsychotic drug action on the corticotropin-releasing hormone (CRH) gene activity has not been investigated so far. This study was undertaken to examine the influence of conventional and atypical antipsychotic drugs on the CRH gene promoter activity in differentiated Neuro-2A cell cultures stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It has been found that chlorpromazine (0.1-5.0 mM), haloperidol (0.5-5.0 mM), clozapine (1.0-5.0 mM), thioridazine (1.0-5.0 mM), promazine (5.0 and 10 mM), risperidone (5.0 and 10.0 mM), and raclopride (only at the highest used concentrations, ie 30 and 100 mM) present in culture medium for 5 days inhibited the CRH-CAT activity. Sulpiride and remoxipride had no effect. Since CRH gene activity is most potently enhanced by cAMP/protein kinase A pathway, the effect of antipsychotics on the forskolin-induced CRH-CAT activity was determined. Chlorpromazine (1.0-5.0 mM), haloperidol (1.0-5.0 mM), clozapine (1.0-5.0 mM), thioridazine (3.0 and 5.0 mM), and raclopride (30 and 100 mM), but not promazine, sulpiride, risperidone, and remoxipride, inhibited the forskolin-stimulated CRH gene promoter activity. A possible involvement of protein kinases in chlorpromazine and clozapine inhibitory action on CRH activity was also investigated. It was found that wortmannin (0.01 and 0.02 mM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K), significantly attenuated the inhibitory effect of chlorpromazine and clozapine on CRH gene promoter activity. In line with these results, a Western blot study showed that these drugs increased phospho-Ser-473 Akt level, had no effect on total Akt, and decreased glycogen synthase kinase-3b level. Additionally, we found that clozapine decreased protein kinase C (PKC) level and that its action on CRH activity was attenuated by PKC activator (TPA, 0.1 mM). The obtained results indicate that inhibition of CRH gene promoter activity by some antipsychotic drugs may be a molecular mechanism responsible for their inhibitory action on HPA axis activity. Clozapine and chlorpromazine action on CRH activity operates mainly through activation of the PI3-K/Akt pathway. Moreover, PKC-mediated pathway seems to be involved in clozapine action on CRH gene activity.

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“…However, this appears not to be the case since anxiolytic doses of BDZs also elevate (dose-dependently) CS concentrations when administered acutely to unstressed rats (16,20,22,27,31). These anxiogenic or prostress effects are generally believed to arise from the sedative/ ataxic actions of BDZs (22,27,31), although such a relationship and Health Research MEDIGON (grant No.…”

Section: Noradrenalinementioning

confidence: 95%

Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats

Boer

Gugten

Slangen

1991

Pharmacology Biochemistry and Behavior

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Plasma corticosterone and brain catecholamines in stress: Effect of psychotropic drugs

Cited by 114 publications

References 21 publications

Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Mechanisms by Which Picrotoxin and a High Dose of Diazepam Elevate Plasma Corticosterone Level

Antipsychotic Drugs Inhibit the Human Corticotropin-Releasing-Hormone Gene Promoter Activity in Neuro-2A Cells—an Involvement of Protein Kinases

Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats

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