A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex

Birnbaum, Shari G.; Gobeske, Kevin T.; Auerbach, Joshua D.; Taylor, Jane R.; Arnsten, Amy F.T.

doi:10.1016/s0006-3223(99)00138-9

Cited by 257 publications

(184 citation statements)

References 40 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…These results indicate that systemic FG-7142 administration disrupts the functional connectivity both within and between mPFC and BLA. Given that FG-7142 mimics several behavioral (Birnbaum et al, 1999;File et al, 1982File et al, , 1985Murphy et al, 1996;Pellow and File, 1986), neuroendocrine Stephens et al, 1987) and autonomic (Berntson et al, 1996;Hart et al, 1998) stress responses modulated by mPFC and BLA (Buijs and van Eden, 2000), it is tempting to speculate that disruption of neuronal network interactions within and between these regions may model certain aspects of corticolimbic dysfunction induced by stressors.…”

Section: Discussionmentioning

confidence: 99%

“…Burst firing in mPFC is diminished by systemic administration of NMDA receptor antagonists, drugs which also disrupt working memory (Homayoun et al, 2005;Jackson et al, 2004). Given that NMDA receptor hypofunction and FG-7142 treatment have similar effects on mPFC bursting and working memory (Birnbaum et al, 1999;Murphy et al, 1996), burst firing in mPFC may play a critical role in mediating cognitive functions such as attention and vigilance (Krahe and Gabbiani, 2004). Similarly, amygdaloid bursts occur in response to affectively relevant stimuli (Nishijo et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…In one group of animals, vehicle (10% cremophor EL in 0.5 ml/kg; Hart et al, 1998) and four doses of 1.0,3.3,10.0 mg/kg in 0.5 ml/kg) were each injected every 3 min. The higher doses in the range used here are comparable to those used in previous studies examining the effects on anxiety-related behavior (Berntson et al, 1996;Birnbaum et al, 1999;File et al, 1982File et al, , 1985Hart et al, 1998;Murphy et al, 1996;File, 1985, 1986;Stephens et al, 1987). Each dose was followed immediately by injection of heparinized saline (50 ml; CP Pharmaceuticals, UK) to flush the cannula and thus ensure that drug was administered completely.…”

Section: Drug Administrationmentioning

confidence: 93%

“…This benzodiazepine receptor partial inverse agonist mimics various behavioral, neuroendocrine, and autonomic stress responses. For example, FG-7142 causes anxiety (File et al, 1982Pellow and File, 1986), impairs working memory (Birnbaum et al, 1999;Murphy et al, 1996), induces corticosterone release Stephens et al, 1987) and potentiates sympathetic arousal (Berntson et al, 1996;Hart et al, 1998). As is the case with other stressors, FG-7142 also increases monoamine metabolism (Bradberry et al, 1991;Dazzi et al, 2002;Ida et al, 1991) and Fos activation (Kurumaji et al, 2003;Singewald et al, 2003) in mPFC and BLA.…”

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

Stevenson

Halliday

Marsden

et al. 2007

Synapse

View full text Add to dashboard Cite

The medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) coordinate various stress responses. Although the effects of stressors on mPFC and BLA activity have been previously examined, it remains unclear to what extent stressors affect functional interactions between these regions. In vivo electrophysiology in the anesthetized rat was used to examine mPFC and BLA activity simultaneously in response to FG-7142, a benzodiazepine receptor partial inverse agonist that mimics various stress responses, in an attempt to model the effects of stressors on corticolimbic functional connectivity. Extracellular unit and local field potential (LFP) recordings, using multielectrode arrays positioned in mPFC and BLA, were conducted under basal conditions and in response to systemic FG-7142 administration. This drug increased mPFC and BLA unit firing at the lowest dose tested, whereas higher doses of FG-7142 decreased various burst firing parameters in both regions. Moreover, LFP power was attenuated at lower (<1 Hz) and potentiated at higher frequencies in mPFC (1-12 Hz) and BLA (4-8 Hz). Interestingly, FG-7142 diminished synchronized unit firing, both within and between mPFC and BLA. Finally, FG-7142 decreased LFP synchronization between these regions. In a separate group of animals, pretreatment with the selective benzodiazepine receptor antagonist flumazenil blocked the changes in burst firing, LFP power and synchronized activity induced by FG-7142, confirming direct benzodiazepine receptor-mediated effects. These results indicate that FG-7142 disrupts corticolimbic network interactions via benzodiazepine receptor partial inverse agonism. Perturbation of mPFC-BLA functional connectivity induced by FG-7142 may provide a useful model of corticolimbic dysfunction induced by stressors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Drug Administrationmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

Stevenson

Halliday

Marsden

et al. 2007

Synapse

View full text Add to dashboard Cite

show abstract

“…The PFC is critical for guiding behavior using working memory (Goldman-Rakic 1987). Our lab has shown that stress impairs working memory performance in rats and monkeys via excessive stimulation of catecholamine receptors (reviewed in Arnsten and Goldman-Rakic 1998;Birnbaum et al 1999). A continuing goal of this research is to identify the receptor subtypes underlying stressinduced PFC deficits.…”

mentioning

confidence: 99%

The Selective Dopamine D4 Receptor Antagonist, PNU-101387G, Prevents Stress-Induced Cognitive Deficits in Monkeys

Arnsten

Murphy

Merchant

2000

Neuropsychopharmacology

View full text Add to dashboard Cite

Stress exposure impairs the cognitive functioning of the prefrontal cortex (PFC). Previous research has examined the dopamine (DA) D1 receptor mechanisms underlying this response. The current study performed a preliminary examination of the role of D4 receptor mechanisms by determining whether the selective D4 receptor antagonist, PNU-101387G, could prevent stress-induced working memory deficits in monkeys. Animals were tested on the delayed response task following treatment with PNU-101387G (0 or 0.1-0.8 mg/kg, 60-min pretreatment), and the pharmacological stressor, FG7142 (0 or 0.2 mg/kg,. Exposure to stress can exacerbate or precipitate neuropsychiatric disorders such as schizophrenia and affective disorders involving deficits in higher cognitive functions (Mazure 1995). Thus, it is important to understand the mechanisms by which stress exposure alters higher cortical function. For years it has been appreciated that even mild stress exposure releases monoamines in the prefrontal cortex (PFC; e.g., Goldstein et al. 1996;Kaneyuki et al. 1991;Thierry et al. 1976). The PFC is critical for guiding behavior using working memory (Goldman-Rakic 1987). Our lab has shown that stress impairs working memory performance in rats and monkeys via excessive stimulation of catecholamine receptors (reviewed in Arnsten and Goldman-Rakic 1998;Birnbaum et al. 1999). A continuing goal of this research is to identify the receptor subtypes underlying stressinduced PFC deficits. FG7142 significantly impaired delayed response performance relative to vehicle; PNU-101387G pretreatment produced a dose-related reversal of the FG7142 response. PNU-101387G had no significant effects on its own, but there were trends toward improvement at low doses and impairment at higher doses. Further studies in a largerThe effects of stress have been examined using spatial working memory paradigms such as the delayed response task which are tightly linked to PFC function in monkeys (Goldman and Rosvold 1970). Exposure to either loud noise stress or to a pharmacological stressor (the inverse benzodiazepine agonist, FG7142) impaired delayed response performance in monkeys (Arnsten and Goldman-Rakic 1998;Murphy et al. 1996). In con- 23 , NO . 4 trast, these same stressors had no effect on discrimination tasks with similar motor and motivational needs that do not rely on PFC function (Arnsten and Goldman-Rakic 1998;Murphy et al. 1996). A similar pattern has been observed in humans, where loud noise stress impaired performance of tasks associated with the PFC such as the Stroop interference task (Hartley and Adams 1974), but facilitated simple or well-rehearsed tasks (reviewed in Broadbent 1971).Much research to date has focused on the dopamine (DA) mechanisms underlying the stress response, as DA release in the PFC appears to be the most reactive of the monoamines to stress exposure (Goldstein et al. 1996). Several lines of evidence indicate that high levels of DA release in the PFC lead to working memory impairment. Stress-induced working memory defic...

show abstract

Association of Residents' Neural Signatures With Stress Resilience During Surgery

et al. 2019

View full text Add to dashboard Cite

IMPORTANCE Intraoperative stressors may compound cognitive load, prompting performance decline and threatening patient safety. However, not all surgeons cope equally well with stress, and the disparity between performance stability and decline under high cognitive demand may be characterized by differences in activation within brain areas associated with attention and concentration such as the prefrontal cortex (PFC). OBJECTIVE To compare PFC activation between surgeons demonstrating stable performance under temporal stress with those exhibiting stress-related performance decline.

show abstract

A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex

Cited by 257 publications

References 40 publications

Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

The Selective Dopamine D4 Receptor Antagonist, PNU-101387G, Prevents Stress-Induced Cognitive Deficits in Monkeys

Association of Residents' Neural Signatures With Stress Resilience During Surgery

Contact Info

Product

Resources

About