Selective depletion of cortical noradrenaline by anti-dopamine beta-hydroxylase–saporin impairs attentional function and enhances the effects of guanfacine in the rat

Milstein, Jean A.; Lehmann, Olivia; Theobald, David E.; Dalley, Jeffrey W.; Robbins, Trevor W.

doi:10.1007/s00213-006-0594-x

Cited by 80 publications

(80 citation statements)

References 37 publications

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“…Though both NE and ACh have been implicated in attentional control, specifically in the area of sustained attention (McGaughy et al, 1996;Robbins, 1997;Sarter and Bruno, 1999;Robbins, 2000;Milstein et al, 2007), the present data suggest a dissociable role of these neuromodulators in prefrontal processing that contributes to shifts of attentional set. The cognitive effects of noradrenergic deafferentation are selective to the ED and produce overly focused attention.…”

Section: Discussionmentioning

confidence: 54%

“…NE-LX animals would often fail to explore the other stimulus attribute in the test of ED for many trials. It is unlikely that the NE-LX rats suffer from a loss of sustained attention as rats with larger NE lesions are unimpaired in standard tests of sustained attention (McGaughy et al, 1997;Milstein et al, 2007). Unpublished data show that similar noradrenergic lesions of the IL/PL produce an insensitivity to cross-modal distraction in a Newman et al, 2006) supporting the hypothesis that the attentional focus of these rats is abnormally narrow and that they persist in responding to a stimulus that previously predicted reinforcement.…”

mentioning

confidence: 86%

“…DBH saporin; 192 IgG saporin; infralimbic/prelimbic cortices; selective attention Studies aimed at understanding the neurochemical basis of attention have found that both norepinephrine (NE) and acetylcholine (ACh) mediate aspects of attention (McGaughy and Sarter, 1995b;McGaughy et al, 1996;Rajkowski et al, 2004;Milstein et al, 2007) but some conditions dissociate the functions of these systems. Yu and Dayan (2005) hypothesize that NE mediates unexpected uncertainty while ACh mediates expected uncertainty.…”

Section: Introductionmentioning

confidence: 99%

“…The current methodology allows restricted depletion of NE while sparing dopaminergic terminals (Wrenn et al, 1996;Milstein et al, 2007). Though the locus coeruleus cell bodies provide widespread innervations of sub-cortical and cortical targets (Foote et al, 1983), recent data from Robbins and colleagues (Milstein et al, 2007) has shown that lesions produced by intracortical infusions of DBH saporin deplete cortical targets while "subcortical structures" are "spared at all levels." These data support the hypothesis that cognitive effects in the current task result from a loss of cortical rather than sub-cortical targets.…”

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confidence: 99%

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Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

2008

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Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward. KeywordsDBH saporin; 192 IgG saporin; infralimbic/prelimbic cortices; selective attention Studies aimed at understanding the neurochemical basis of attention have found that both norepinephrine (NE) and acetylcholine (ACh) mediate aspects of attention (McGaughy and Sarter, 1995b;McGaughy et al., 1996;Rajkowski et al., 2004;Milstein et al., 2007) but some conditions dissociate the functions of these systems. Yu and Dayan (2005) hypothesize that NE mediates unexpected uncertainty while ACh mediates expected uncertainty. In other words, there exists some known ambiguity in many attentional situations, e.g. spatial or temporal unpredictability of targets, and variability in perceptual attributes of target (Chiba et al., 1995;McGaughy and Sarter, 1995a;Bucci et al., 1998;McGaughy et al., 2002;Maddux et al., 2007). After acquisition, this uncertainty though not predictable is known, expected, and requires ACh Dayan, 2002, 2005). Additionally, unexpected uncertain events may occur, e.g. changes in reinforcement contingencies in a well-learned task, and recruit NE (Robbins, 2000;Dalley et al., 2001; Sara, 2004, 2005;Dalley et al., 2004;Yu and Dayan, 2005 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThough these frameworks are useful there remains ambiguity about the attentional situations that require ACh and those that require NE. This ambiguity may result from a reliance on data obtained from manipulations of the cell bodies of these systems (Aston-Jones et al., 1994, 2000McGaughy et al., 1996McGaughy et al., , 2002. Both NE and ACh innervate much of the neocortical mantle so previous frameworks posited a unita...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

2008

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“…Given the prominent role of NE in the Stop process (Eagle et al, 2007), the stressinduced increase in SSRT to Alcohol words could derive from high tonic NE transmission (Abercrombie and Jacobs, 1987), which would be expected to impede effortful, sustained attention (Milstein et al, 2007), particularly when the discriminative stimuli are highly salient (Ventura et al, 2008). In sum, the interaction of stress and Alcohol cues in this study suggests the operation of two interdependent processes: involuntary recruitment of attention by salient Go stimuli possibly mediated by phasic DA, and a stressinduced decrease in sustained attention to unpredictable Stop stimuli that call for inhibition, likely mediated by high tonic NE.…”

Section: Stress and Alcohol Cues On Go-stop Responding M Zack Et Almentioning

confidence: 99%

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

Zack

Woodford

Tremblay

et al. 2010

Neuropsychopharmacol

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Stress, cues, and pharmacological priming are linked with relapse to addictive behavior. Increased salience and decreased inhibitory control are thought to mediate the effects of relapse-related stimuli. However, the functional relationship between these two processes is unclear. To address this issue, a modified Stop Signal Task was employed, which used Alcohol, Neutral, and Non-Words as Go stimuli, and lexical decision as the Go response. Subjects were 38 male problem drinkers (mean Alcohol Dependence Scale (ADS) score: 18.0). Uncontrollable noise (B10 min at 110 dB) was the stressor; nonalcoholic placebo beer (P-Beer) was the cue manipulation, and alcohol (0.7 g/kg), the pharmacological prime. Half the sample received alcohol, and half P-Beer. Stress and beverage (test drink vs soft drink) were manipulated within subjects on two sessions, with half the sample receiving active manipulations together and half receiving them separately. Go response time (RT) and Stop Signal RT (SSRT) were slower to Alcohol than Neutral words. Stress augmented this bias. Alcohol and P-Beer impaired overall SSRT. Stress impaired neither overall SSRT nor Go RT. SSRT to Neutral words and Non-Words correlated inversely with Go RT to Alcohol and Neutral words, and Non-Words. ADS correlated directly with SSRT to Alcohol words. A resource allocation account was proposed, whereby diversion of limited resources to salient cues effectively yoked otherwise independent Go and Stop processes. Disturbances of prefrontal norepinephrine and dopamine were cited as possibly accounting for these effects. Treatments that optimize prefrontal catecholamine transmission may deter relapse by reducing disinhibitory effects of salient eliciting stimuli.

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2008

Hepatology

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Selective depletion of cortical noradrenaline by anti-dopamine beta-hydroxylase–saporin impairs attentional function and enhances the effects of guanfacine in the rat

Cited by 80 publications

References 37 publications

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

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