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B Roozendaal

Publications and source records attributed to B Roozendaal.

At least 19 recordsLinked to original sources
PubMed2006

Do corticosteroids damage the brain?

Corticosteroids are an essential component of the body's homeostatic system. In common with other such systems, this implies that corticosteroid levels in blood and, more importantly, in the tissues remain within an optimal range. It also implies that this range may vary according to circumstance. Lack of corticosteroids, such as untreated Addison's disease, can be fatal in humans. In this review, we are principally concerned with excess or disturbed patterns of circulating corticosteroids in the longer or shorter term, and the effects they have on the brain.

Adrenal Cortex Hormones↗
PubMed2005

Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions.

Extensive evidence from rat and human studies indicates that glucocorticoid hormones influence cognitive performance. Posttraining activation of glucocorticoid-sensitive pathways dose-dependently enhances the consolidation of long-term memory. Glucocorticoid effects on memory consolidation rely on noradrenergic activation of the basolateral amygdala and interactions of the basolateral amygdala with other brain regions. Glucocorticoids interact with the noradrenergic system both at a postsynaptic level, increasing the efficacy of the beta-adrenoceptor-cyclic AMP/protein kinase A system, as well as presynaptically in brainstem noradrenergic cell groups that project to the basolateral amygdala. In contrast, memory retrieval and working memory performance are impaired with high circulating levels of glucocorticoids. Glucocorticoid-induced impairment of these two memory functions also requires the integrity of the basolateral amygdala and the noradrenergic system. Such critical interactions between glucocorticoids and noradrenergic activation of the basolateral amygdala have important consequences for the role of emotional arousal in enabling glucocorticoid effects on these different memory functions.

Amygdala↗
PubMed2001

The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors.

BACKGROUND: Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors. Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration. This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors. METHODS: Patients (n = 20) were recruited from a prospective, randomized double-blind study on the hemodynamic effects of hydrocortisone during septic shock. Eleven patients had received placebo and nine stress doses of hydrocortisone. Posttraumatic stress disorder was diagnosed 31 months (median) after intensive care unit discharge using SCID-IV (DSM-IV-criteria). Furthermore, the number of categories of traumatic memory from ICU treatment was determined in both groups at that time. RESULTS: Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder, compared with seven of 11 patients in the placebo group (p =.02). There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups. CONCLUSIONS: The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors, which seems to be independent of the number of categories of traumatic memory.

Adult↗
PubMed2001

Basolateral amygdala-nucleus accumbens interactions in mediating glucocorticoid enhancement of memory consolidation.

Systemic or intracerebral administration of glucocorticoids enhances memory consolidation in several tasks. Previously, we reported that these effects depend on an intact basolateral nucleus of the amygdala (BLA) and efferents from the BLA that run through the stria terminalis (ST). The BLA projects directly to the nucleus accumbens (NAc) via this ST pathway. The NAc also receives direct projections from the hippocampus and, therefore, may be a site of convergence of BLA and hippocampal influences in modulating memory consolidation. In support of this view, we found previously that lesions of either the NAc or the ST also block the memory-modulatory effect of systemically administered glucocorticoids. The present experiments examined the effects of lesions of the NAc or the ST on the memory-modulatory effects of intracerebral glucocorticoids on inhibitory avoidance training. Microinfusions of the specific glucocorticoid receptor agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 1.0 or 3.0 ng) into either the BLA or the hippocampus of male Sprague Dawley rats administered immediately after training enhanced the 48 hr retention performance in a dose-dependent manner. Bilateral lesions of the NAc or the ST alone did not affect retention performance but blocked the memory enhancement induced by intra-BLA or intrahippocampal glucocorticoid receptor agonist administration. These findings indicate that the BLA-NAc pathway plays an essential role in mediating glucocorticoid effects on memory consolidation and suggest that the BLA interacts with hippocampal effects on memory consolidation via this pathway.

Amygdala↗
PubMed2001

Memory retrieval impairment induced by hippocampal CA3 lesions is blocked by adrenocortical suppression.

There is evidence that in rats, partial hippocampal lesions or selective ablation of the CA3 subfield can disrupt retrieval of spatial memory and that hippocampal damage disinhibits hypothalamic-pituitary-adrenocortical (HPA)-axis activity, thereby elevating plasma levels of adrenocorticotropin and corticosterone. Here we report evidence that attenuation of CA3 lesion-induced increases in circulating corticosterone levels with the synthesis inhibitor metyrapone, administered shortly before water-maze retention testing, blocks the impairing effects of the lesion on memory retrieval. These findings suggest that elevated adrenocortical activity is critical in mediating memory retrieval deficits induced by hippocampal damage.

Adrenal Cortex↗
PubMed2000

Sparing of neuronal function postseizure with gene therapy.

Numerous studies have demonstrated that gene therapy interventions can protect neurons from death after neurological insults. In nearly all such studies, however, "protection" consists of reduced neurotoxicity, with no demonstrated preservation of neuronal function. We used a herpes simplex virus-1 system to overexpress either the Glut-1 glucose transporter (GT) (to buffer energetics), or the apoptosis inhibitor Bcl-2. Both decreased hippocampal neuron loss to similar extents during excitotoxic insults in vitro and in vivo. However, the mediating mechanisms and consequences of the two interventions differed. GT overexpression attenuated early, energy-dependent facets of cell death, blocking oxygen radical accumulation. Bcl-2 expression, in contrast, blocked components of death downstream from the energetic and oxidative facets. Most importantly, GT- but not Bcl-2-mediated protection preserved hippocampal function as assessed spatial maze performance. Thus, gene therapeutic sparing of neurons from insult-induced death does not necessarily translate into sparing of function.

Animals↗
PubMed2000

1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation.

This paper summarizes recent findings on the amygdala's role in mediating acute effects of glucocorticoids on memory consolidation in rats. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors (GRs or type II) enhances memory consolidation in a dose-dependent inverted-U fashion. Selective lesions of the basolateral nucleus of the amygdala (BLA) or infusions of beta-adrenoceptor antagonists into the BLA block the memory-modulatory effects of systemic injections of glucocorticoids. Additionally, posttraining infusions of a specific GR agonist administered directly into the BLA enhance memory consolidation, whereas those of a GR antagonist impair. These findings indicate that glucocorticoid effects on memory consolidation are mediated, in part, by an activation of GRs in the BLA and that the effects require beta-adrenergic activity in the BLA. Other findings indicate that the BLA interacts with the hippocampus in mediating glucocorticoid-induced modulatory influences on memory consolidation. Lesions of the BLA or inactivation of beta-adrenoceptors within the BLA also block the memory-modulatory effects of intrahippocampal administration of a GR agonist or antagonist. These findings are in agreement with the general hypothesis that the BLA integrates hormonal and neuromodulatory influences on memory consolidation. However, the BLA is not a permanent locus of storage for this information, but modulates consolidation processes for explicit/associative memories in other brain regions, including the hippocampus.

Amygdala↗
PubMed2000

Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonism in the basolateral amygdala.

Glucocorticoid-induced memory enhancement is known to depend on beta-adrenoceptor activation in the basolateral amygdala (BLA). Additionally, inactivation of muscarinic cholinergic receptors in the rat amygdala blocks memory enhancement induced by concurrent beta-adrenergic activation. Together, these findings suggest that glucocorticoid-induced modulation of memory consolidation requires cholinergic as well as adrenergic activation in the BLA. Two experiments investigated this issue. The first experiment examined whether blockade of muscarinic cholinergic receptors in the BLA with atropine alters the memory-enhancing effects of the systemically administered glucocorticoid dexamethasone. Dexamethasone (0.3, 1.0 or 3.0 mg/kg, s.c.) administered to rats immediately after inhibitory avoidance training produced dose-dependent enhancement of 48-h retention. Concurrent bilateral infusions of the muscarinic cholinergic antagonist atropine (0.5 microg in 0.2 microL per side) into the BLA blocked the memory enhancement. The second experiment investigated whether the BLA is a locus of interaction between glucocorticoid and muscarinic activation. The specific glucocorticoid receptor (GR or type II) agonist RU 28362 (1.0, 3.0 or 10 ng) was infused into the BLA either alone or together with atropine immediately after training. The GR agonist produced dose-dependent memory enhancement and atropine blocked the memory enhancement. These findings indicate that muscarinic cholinergic activation within the BLA is critical for enabling glucocorticoid enhancement of memory consolidation and that enhancement of memory induced by GR activation in the BLA requires cholinergic activation within the BLA.

Acetylcholine↗
PubMed2000

Involvement of a basolateral amygdala complex-nucleus accumbens pathway in glucocorticoid-induced modulation of memory consolidation.

Systemic or intracerebral administration of glucocorticoids modulates memory consolidation in several tasks. Previously, we have shown that these memory-modulatory effects depend on an intact basolateral complex of the amygdala (BLC) and efferents from the BLC that run through the stria terminalis. It is currently unknown, however, what BLC efferent structures mediate these effects. The present experiments were designed to determine whether the nucleus accumbens (NA), which receives BLC efferents through the stria terminalis and is involved in several BLC-dependent behaviours, is involved in glucocorticoid-induced modulation of memory consolidation. In experiment 1, rats with bilateral sham or N-methyl-D-aspartate (NMDA)-induced lesions of the NA were trained on a one-trial, footshock-motivated inhibitory avoidance task, and given immediate post-training injections of either the synthetic glucocorticoid dexamethasone (0.3 or 1.0 mg/kg, s.c.) or vehicle. Testing 48 h later revealed that dexamethasone significantly enhanced retention in sham-lesioned rats but that the enhancing effect was blocked in NA-lesioned rats. An asymmetrical, or crossed-lesion design was employed in experiment 2. Rats with a unilateral NMDA-induced lesion of the BLC and a unilateral lesion of either the ipsilateral or contralateral NA were trained as in experiment 1. Testing 48 h later revealed that dexamethasone enhanced retention in ipsilaterally lesioned rats, but that this effect was blocked in contralaterally lesioned rats. These findings indicate that an intact BLC-NA pathway is critical for the enhancing effects of glucocorticoids on memory consolidation, and are consistent with the view that the BLC regulates memory consolidation in other brain regions.

Amygdala↗
PubMed1999

Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: a critical involvement of the amygdala.

There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. Infusions of norepinephrine or beta-adrenoceptor agonists into the BLA enhance memory for inhibitory avoidance as well as water maze training. Other findings show that alpha 1-adrenoceptor activation also enhances memory for inhibitory avoidance training through an interaction with beta-adrenergic mechanisms. The central hypothesis guiding the research reviewed in this chapter is that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from experiments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorticoids are mediated by influences involving activation of beta-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates explicit/declarative memory storage in other brain regions.

Adrenal Cortex Hormones↗
PubMed1999

Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation.

Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala (BLA) block the enhancing effects of posttraining systemic or intrahippocampal glucocorticoid administration on memory for inhibitory avoidance training. The present study further examined the basis of this permissive influence of the BLA on hippocampal memory functioning. Immediate posttraining unilateral infusions of the specific glucocorticoid receptor agonist RU 28362 (11beta,17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20-yn-3-one; 3.0, 10.0, or 30.0 ng in 0.5 microliter) administered into the dorsal hippocampus of male Sprague-Dawley rats induced dose-dependent enhancement of 48-h inhibitory avoidance retention. Infusions of the beta-adrenoceptor antagonist atenolol (0.5 microgram in 0.2 microliter) into the ipsilateral, but not the contralateral, BLA 10 min prior to training blocked the hippocampal glucocorticoid effects on memory consolidation. Infusions of the muscarinic cholinergic antagonist atropine (0.5 microgram in 0.2 microliter) into either the ipsilateral or contralateral BLA before training did not block the hippocampal glucocorticoid effects. These findings provide further evidence that beta-adrenergic activity in the BLA is essential in enabling glucocorticoid-induced modulation of memory consolidation and are consistent with the hypothesis that the BLA regulates the strength of memory consolidation in other brain structures. The ipsilateral nature of the BLA-hippocampus interaction indicates that BLA influences on hippocampal memory processes are mediated through neural pathways rather than by influences by means of the activation of peripheral stress responses.

Amygdala↗
PubMed1999

Basolateral amygdala noradrenergic influences on memory storage are mediated by an interaction between beta- and alpha1-adrenoceptors.

Extensive evidence indicates that norepinephrine modulates memory storage through an activation of beta-adrenoceptors in the basolateral nucleus of the amygdala (BLA). Recent findings suggest that the effects of beta-adrenergic activation on memory storage are influenced by alpha1-adrenoceptor stimulation. Pharmacological findings indicate that activation of postsynaptic alpha1-adrenoceptors potentiates beta-adrenoceptor-mediated activation of cAMP formation. The present study examined whether inactivation of alpha1-adrenoceptors in the BLA would alter the dose-response effects on memory storage of intra-BLA infusions of a beta-adrenoceptor agonist, as well as that of a synthetic cAMP analog. Male Sprague Dawley rats received bilateral microinfusions into the BLA of either the beta-adrenoceptor agonist clenbuterol (3-3000 pmol in 0.2 microliter) or 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cAMP) (0.2-7 nmol in 0.2 microliter) alone or together with the alpha1-adrenoceptor antagonist prazosin (0.2 nmol) immediately after training in an inhibitory avoidance task. Retention was tested 48 hr later. Clenbuterol induced a dose-dependent enhancement of retention, and prazosin attenuated the dose-response effects of clenbuterol. Posttraining intra-BLA infusions of 8-bromo-cAMP also induced a dose-dependent enhancement of retention latencies. However, concurrent infusion of prazosin did not alter the dose-response effects of 8-bromo-cAMP. These findings are consistent with the view that alpha1-adrenoceptors affect memory storage by modulating beta-adrenoceptor activation in the BLA. Moreover, these findings are consistent with those of pharmacological studies indicating that beta-adrenoceptors modulate memory storage by a direct coupling to adenylate cyclase, whereas alpha1-receptors act indirectly by influencing the beta-adrenoceptor-mediated influence on cAMP formation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Involvement of alpha1-adrenoceptors in the basolateral amygdala in modulation of memory storage.

These experiments examined the involvement of alpha1-adrenoceptors in the basolateral amygdala and their interaction with beta-adrenoceptors in modulating memory storage. In Experiment 1, male Sprague-Dawley rats, implanted with bilateral cannulae in the basolateral amygdala, were trained in a one-trial inhibitory avoidance task and immediately after training, were given microinfusions (0.2 microl/side) of the selective alpha1-adrenoceptor antagonist, prazosin (0.1-1.0 microg). Retention was tested 48 h later. Prazosin induced a dose-dependent impairment in retention performance. In Experiment 2, animals received post-training intra-basolateral amygdala infusions of phenylephrine (a non-selective alpha-adrenoceptor agonist; 1.0-10.0 microg) alone or in combination with yohimbine (a selective alpha2-adrenoceptor antagonist; 0.2 microg) to examine the effects, on memory storage, of selective alpha1-adrenoceptor activation. Low doses of phenylephrine alone tended to impair retention performance, whereas the highest dose was non-effective. In contrast, phenylephrine infused together with yohimbine induced a dose-dependent enhancement of retention performance, suggesting that a selective activation of alpha1-adrenoceptors enhances memory formation. In Experiment 3, animals received intra-basolateral amygdala infusions of phenylephrine (1.0-10.0 microg) and yohimbine (0.2 microg) in combination with atenolol (a beta1-adrenoceptor antagonist; 1.0 microg). Atenolol blocked the memory-enhancing effects induced by infusions of phenylephrine together with yohimbine. Considered together, these findings suggest that alpha1-adrenoceptors in the basolateral amygdala are implicated in mediating the effects of norepinephrine on memory storage and that their action depends on concurrent beta-adrenoceptor activation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Microinfusions of flumazenil into the basolateral but not the central nucleus of the amygdala enhance memory consolidation in rats.

Extensive evidence indicates that benzodiazepine receptors in the amygdala are involved in regulating memory consolidation. Recent findings indicate that many other drugs and hormones influence memory through selective activation of the basolateral amygdala nucleus (BLA). This experiment examined whether the memory-modulatory effect of flumazenil, a benzodiazepine receptor antagonist, selectively involves the BLA. Bilateral microinfusions of flumazenil (12 nmol in 0.2 microl) into the BLA of rats administered immediately after training in an inhibitory avoidance task significantly enhanced 48-h retention performance whereas infusions into the central nucleus were ineffective. These findings indicate that the BLA is selectively involved in mediating flumazenil's influence on memory storage and are thus consistent with extensive evidence indicating that the BLA is involved in regulating memory consolidation.

Amygdala↗
PubMed1999

Glucocorticoid receptor activation in the rat nucleus of the solitary tract facilitates memory consolidation: involvement of the basolateral amygdala.

These experiments examined the involvement of glucocorticoid receptors (GRs or type II) located in the A2-noradrenergic cell group of the rat nucleus of the solitary tract (NTS) in modulating memory storage. Bilateral intra-NTS infusions (0.5 microL) of the specific GR agonist RU 28362 (11beta, 17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one), in doses ranging from 0.01 to 10.0 ng, immediately after inhibitory avoidance training produced a dose-dependent enhancement of 48 h retention performance. Infusions of 0.1 or 1.0 ng of the agonist enhanced retention, whereas lower or higher doses were ineffective. Post-training infusions of the GR antagonist RU 38486 [17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(1-pr opynyl)-o estra-4,9-dien-3-one, 0.01-10.0 ng] into the NTS did not significantly affect retention performance, but shifted the dose-response effects of post-training systemic injections of the synthetic glucocorticoid dexamethasone to the right. These results indicate that activation of GRs in the NTS can influence memory formation for inhibitory avoidance training, and suggest that the effects of circulating glucocorticoids on memory are mediated, in part, by an activation of GRs in the NTS. Additionally, pretraining infusions of the beta1-adrenergic antagonist atenolol (0.5 microg in 0.2 microL) into the basolateral nucleus of the amygdala (BLA), a brain structure which receives noradrenergic projections from the NTS and is implicated in memory storage modulation, blocked the memory-enhancing effects of the GR agonist (1.0 ng) infused into the NTS. These findings provide evidence that memory storage is modulated by glucocorticoid binding to GRs in noradrenergic cell bodies in the NTS and suggest that these modulatory effects are conveyed by ascending projections to the BLA.

Amygdala↗
PubMed1998

Norepinephrine release in the amygdala in response to footshock and opioid peptidergic drugs.

These experiments used in vivo microdialysis and high-performance liquid chromatography to examine, in rats, norepinephrine (NE) release in the amygdala induced by footshock and systemic administration of drugs affecting the opioid peptidergic system. A microdialysis probe was inserted into a previously implanted guide cannula aimed at the amygdala and the rat was placed in a box with a stainless-steel grid floor through which a single footshock was delivered. Samples were collected and analyzed at 15-min intervals. Footshock stimulation increased NE levels and the magnitude of the increase varied with footshock intensity. Relative to baseline levels, intensities of 0.3, 0.7 and 1.2 mA (3 s) induced increases of 41, 64 and 97%, respectively. NE levels returned to baseline within 30 min after footshock stimulation. The opioid peptidergic antagonist naloxone (1 mg/kg, i.p.) administered immediately after footshock (0.55 mA for 1 s) potentiated NE release. In contrast, the opioid peptidergic agonist beta-endorphin (10 microgram/kg, i.p.) administered after the footshock blocked the footshock-induced increase in NE levels. The magnitude of NE release was less when the drugs were administered without prior footshock and when the injections were given 30 min after footshock. The findings are consistent with previous evidence that acute, mildly stressful stimulation induces the release of NE in the amygdala as well as with extensive pharmacological evidence indicating that amygdala NE released by arousing stimulation is involved in regulating memory storage and that the opioid peptidergic system influences memory storage by modulating the release of NE in the amygdala.

Amygdala↗