Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain.

Härfstrand, Anders; Fuxé, Kjell; Cintra, A.; Agnati, Luigi F.; Zini, Isabella; Wikström, Ann Charlotte; Okret, Sam; Yu, Zhongjian; Goldstein, Menek; Steinbusch, Harry

doi:10.1073/pnas.83.24.9779

Cited by 394 publications

(194 citation statements)

References 23 publications

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“…Here again, we have not detected a significant effect of dexamethasone on the stressinduced c-Fos expression on the lateral septum that has a high density of type II receptors (Magariños et al, 1989). On the other hand, we observed an effect of dexamethasone on the LC that has high reactivity to glucocorticoid receptors (Härfstrand et al, 1986).…”

Section: Dexamethasonecontrasting

confidence: 54%

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Medeiros

Reis

Mello

2005

Neuropsychopharmacol

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Immobilization stress upregulates c-Fos expression in several CNS areas. Repeated stress or the use of drugs can modulate stressinduced c-Fos expression. Here, we investigated in 40 different areas of the rat brain the effects of dexamethasone (SDX, a synthetic glucocorticoid), diazepam (SBDZ, a benzodiazepine), and imipramine (IMI, an antidepressant) on the c-Fos expression induced by restraint stress. Wistar rats were divided into four groups and submitted to 20 days of daily injection of saline (three first groups) or imipramine, 15 mg/kg, i.p. On day 21, animals were submitted to injections of saline (somatosensory, SS), SDX (1 mg/kg, i.p.), SBDZ (5 mg/kg, i.p.), or IMI (15 mg/kg, i.p.) before being submitted to restraint. Immediately after stress, the animals were perfused and their brains processed with immunohistochemistry for c-Fos (Ab-5 Oncogene Science). Dexamethasone reduced stress-induced c-Fos expression in SS cortex, hippocampus, paraventricular nucleus of the hypothalamus (PVH), and locus coeruleus (LC), whereas diazepam reduced c-Fos staining in the SS cortex, hippocampus, bed nucleus of stria terminalis, septal area, and hypothalamus (preoptic area and supramammillary nucleus). Chronic administration of imipramine decreased staining in the hippocampus, PVH, and LC, while increasing it in the nucleus raphe pallidus. We conclude that dexamethasone, diazepam and imipramine differentially modulate stress-induced Fos expression. The present study provides an important comparative background that may help in the further understanding of the effects of these compounds and on the brain activation as well as on the behavioral, neuroendocrine, and autonomic responses to stress.

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Section: Dexamethasonecontrasting

confidence: 54%

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Medeiros

Reis

Mello

2005

Neuropsychopharmacol

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“…Glucocorticoid receptors are localized in brain monoaminergic neurons, particularly in the ventral tegmental (Härfstrand et al 1986), and these receptors have pivotal regulatory roles in many regions of the brain (De Kloet 1991; Joels and de Kloet 1992, 1994). Direct cellular interactions between stress hormones and dopamine neurons have been difficult to document; however, glucocorticoids can interact with dopamine reward circuitry in the basal forebrain that may be independent of direct glucocorticoid/dopamine interactions.…”

Section: Individual Differences and Rewardmentioning

confidence: 99%

“…Such stress hormones, via alterations of neuronal activity, consequently can induce neurobehavioral pathology. As noted above, dopaminergic neurons have receptors for glucocorticoids (Härfstrand et al 1986), and increases in the circulating levels of the hormones induce an increase of dopamine utilization in mesocorticolimbic neurons, an effect that is state-dependent (i.e., higher during the dark phase, or during food intake) (Piazza and Le Moal 1997). Thus, increases in corticosteroids renders animals more vulnerable to the acute reinforcing effects of drugs of abuse (Piazza and Le Moal 1997).…”

mentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,544

1,962

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This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

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“…Corticosterone administration has been shown to increase basal release of dopamine (DA) in the nucleus accumbens (Piazza et al, 1996b), whereas adrenalectomy reduces basal extracellular DA levels and blunts COC-induced DA increase in the same brain structure (Barrot et al, 2000). Evidence of a direct interaction between mesolimbic DAergic system and the HPA axis is further emphasized by the fact that glucocorticoid receptors (GRs) are expressed by DAergic neurons (Harfstrand et al, 1986) and that a glucocorticoid-responsive element (GRE) is found in the promoter region of the mouse tyrosine hydroxylase gene (Hagerty et al, 2001a, b).…”

mentioning

confidence: 99%

Effects of Cocaine on c-Fos and NGFI-B mRNA Expression in Transgenic Mice Underexpressing Glucocorticoid Receptors

St-Hilaire

Tremblay

Lévesque

et al. 2002

Neuropsychopharmacol

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Numerous evidences suggest that stress and stress-related hormones can modulate the activity of the brain reward pathway and thus may account for individual vulnerability towards the reinforcing effects of drugs of abuse. Transgenic (TG) mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, were used to assess the role of GR dysfunction on cocaine (COC)-induced c-fos and Nerve-Growth Factor Inducible-B (NGFI-B, or Nur77) gene expression. These two genes belong to different families of transcription factors and have been shown to be modulated by various dopaminergic drugs. TG and wild-type (WT) mice were both acutely and repeatedly treated with COC (20 mg/kg, i.p.). In the chronic experiment, mice received a 5-day treatment of COC and were challenged 5 days later with COC or vehicle. Locomotor activity was assessed during the entire chronic experiment in the mouse home cages. Animals were sacrificed 1 h after the last injection and NGFI-B and c-fos mRNA levels in the prefrontal cortex, the nucleus accumbens and the striatum were measured by in situ hybridization. Acute COC administration led to significantly smaller c-fos increases in TG mice compared to WT, whereas repeated COC treatment potentiated c-fos induction both in TG and WT mice to equivalent levels. TG mice displayed higher basal NGFI-B expression in the nucleus accumbens and the level of NGFI-B mRNA was differently modulated by COC in TG mice compared to WT mice. In accordance with data on c-fos expression, behavioral data indicate a blunted locomotor effect on the first COC injection in TG mice, a phenomenon corrected by the repeated COC treatment. These results suggest that an alteration of the hypothalamus-pituitary-adrenal axis can modify COC-induced regulation of the transcription factors c-fos and NGFI-B, and that these changes parallel those seen at the behavioral level. It also demonstrates that the differences at the behavioral and molecular levels noted between TG and WT mice after acute COC injection disappear following repeated COC administration, suggesting that repeated COC has a greater impact in TG mice underexpressing GRs.

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Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain.

Cited by 394 publications

References 23 publications

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine

Drug Addiction, Dysregulation of Reward, and Allostasis

Effects of Cocaine on c-Fos and NGFI-B mRNA Expression in Transgenic Mice Underexpressing Glucocorticoid Receptors

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