α2- and β-adrenoceptors involvement in nortriptyline modulation of auditory sustained attention and impulsivity

Roychowdhury, Swagata; Peña-Contreras, Zulma; Tam, J. Y. C.; Yadlapalli, Amulya; Dinh, Lu; Nichols, Justin A.; Basu, Debarshi; Atzori, Marco

doi:10.1007/s00213-012-2635-y

Cited by 9 publications

(6 citation statements)

References 59 publications

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“…Consistent with our findings, previous studies suggest that prazosin has little effect on motor impulsivity (Koskinen et al 2003; Liu et al 2009; Milstein et al 2010; Roychowdhury et al 2012). While guanfacine has been reported to decrease impulsive choice in primates (Kim et al 2012), our results are consistent with those from a recent study showing that guanfacine had no effect on decision making in rats (Pardey et al 2013).…”

Section: Discussionsupporting

confidence: 93%

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

2014

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Rationale Stress-induced disruption of decision making has been hypothesized to contribute to drug-seeking behaviors and addiction. Noradrenergic signaling plays a central role in mediating stress responses. However, the effects of acute stress on decision making, and the role of noradrenergic signaling in regulating these effects, have not been well characterized. Objective To characterize changes in decision making caused by acute pharmacological stress, the effects of yohimbine (an α2-adrenergic antagonist) were examined in a delay discounting task. Noradrenergic contributions to decision making were further characterized by examining the effects of propranolol (a β antagonist), prazosin (an αl antagonist), and guanfacine (an α2 agonist). Methods Sprague-Dawley rats were administered drugs prior to performance on a delay discounting task, in which the delay preceding the large reward increased within each session (ascending delays). To dissociate drug-induced changes in delay sensitivity from behavioral inflexibility, drug effects were subsequently tested in a modified version of the discounting task, in which the delay preceding the large reward decreased within each session (descending delays). Results Yohimbine increased choice of the large reward when tested with ascending delays but decreased choice of the same large reward when tested with descending delays, suggesting that drug effects could be attributed to perseverative choice of the lever preferred at the beginning of the session. Propranolol increased choice of the large reward when tested with ascending delays. Prazosin and guanfacine had no effect on reward choice. Conclusions The stress-like effects of yohimbine administration may impair decision making by causing inflexible, perseverative behavior.

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Section: Discussionsupporting

confidence: 93%

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

2014

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“…An oft found bell-shaped dependence of specific PFC-dependent performance on adrenergic activation (Roychowdhury et al, 2012; Sapolsky, 2015) could be interpreted as a transition from a low-energy state (state 2: quiet wake ), to state 3 ( active wake ), associated with a larger energy mobilization, stronger engagement, and improved cognitive performance (left part of the bell shape curve). At the right end of the curve would lay the transition between state 3 ( stress ) and state 4 ( FoF , right part of the bell shape), with a massive engagement of βRs in the cortex as well as in subcortical nuclei—particularly the amygdala—and consequent dysfunctional working memory, in favor of an optimal impulsive, automatic, motor response and full-fledged autonomic sympathetic response (Bouret and Sara, 2005; Hains and Arnsten, 2008; Gamo and Arnsten, 2011).…”

Section: Lc-cns Interactionsmentioning

confidence: 99%

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

Atzori

Cuevas-Olguín

Esquivel-Rendón

et al. 2016

Front. Synaptic Neurosci.

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117

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Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented—in order of decreasing affinity for the catecholamine—by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing—in turn—a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines.

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“…It is known that NE brain levels are important for maintaining sustained attention in time, and it has been shown that low dose of nortryptiline (NE reuptake blocker) can improve the performance of rats in an auditory sustained attention tasks (Roychowdhury et al, 2012). In this line, the additional effect of repeated restraint stress could be unmasked by reboxetine (Figure 3), which might diminish the impairment in performance produced by sustained attention.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, it is possible that chronic stress influences attention via an additional mechanism to the NE system. The auditory pathway and mPFC are strongly regulated by cholinergic system to support sustained attention (Young et al, 2004; Schofield et al, 2011; Roychowdhury et al, 2012; Poorthuis and Mansvelder, 2013; Bloem et al, 2014). It has been reported that A1, MGN, and mPFC receive cholinergic innervation from the basal forebrain and acetylcholine modulates the neuronal activity of these brain areas during attention (Passetti et al, 2000; Kamke et al, 2005; Schofield et al, 2011; Bloem et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats

Pérez-Valenzuela

Gárate‐Pérez

Sotomayor‐Zárate

et al. 2016

Front. Neural Circuits

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Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle-treated animals. These results indicate that NE has a key role in A1 and attention of stressed rats during tone discrimination.

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α2- and β-adrenoceptors involvement in nortriptyline modulation of auditory sustained attention and impulsivity

Cited by 9 publications

References 59 publications

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats

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