Amy Arnsten

Yale University | YU

The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K(+) channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are inc...

Cognitive deficits in psychiatric and age-related disorders generally involve dysfunction of the dorsolateral prefrontal cortex (dlPFC), but there are few treatments for these debilitating symptoms. Group II metabotropic glutamate receptors (mGluR2/3), which couple to Gi/Go, have been a focus of therapeutics based on rodent research, where mGluR2/3...

Schizophrenia is characterized by profound cognitive deficits that are not alleviated by currently available medications. Many of these cognitive deficits involve dysfunction of the newly evolved, dorsolateral prefrontal cortex (dlPFC). The brains of patients with schizophrenia show evidence of dlPFC pyramidal cell dendritic atrophy, likely reducti...

Medications to treat cognitive disorders are increasingly needed, yet researchers have had few successes in this challenging arena. Cognitive abilities in primates arise from highly evolved N-methyl-d-aspartate (NMDA) receptor circuits in layer III of the dorsolateral prefrontal cortex. These circuits have unique modulatory needs that can differ fr...

The prefrontal cortex (PFC) provides top-down regulation of behavior, cognition, and emotion, including spatial working memory. However, these PFC abilities are greatly impaired by exposure to acute or chronic stress. Chronic stress exposure in rats induces atrophy of PFC dendrites and spines that correlates with working memory impairment. As simil...

A variety of cognitive disorders are worsened by stress exposure and involve dysfunction of the newly evolved prefrontal cortex (PFC). Exposure to acute, uncontrollable stress increases catecholamine release in PFC, reducing neuronal firing and impairing cognitive abilities. High levels of noradrenergic α1-adrenoceptor and dopaminergic D1 receptor...

The prefrontal cortex (PFC) elaborates and differentiates in primates, and there is a corresponding elaboration in cortical dopamine (DA). DA cells that fire to both aversive and rewarding stimuli likely project to the dorsolateral PFC (dlPFC), signaling a salient event. Since 1979, we have known that DA has an essential influence on dlPFC working...

Cognitive disorders such as schizophrenia and Alzheimer's disease are associated with dysfunction of the highly evolved dorsolateral prefrontal cortex (dlPFC), and with changes in glutamatergic N-methyl-D-aspartate receptors (NMDARs). Recent research on the primate dlPFC discovered that the pyramidal cell circuits that generate the persistent firin...

Psychiatric disorders such as schizophrenia are worsened by stress, and working memory deficits are often a central feature of illness. Working memory is mediated by the persistent firing of prefrontal cortical (PFC) pyramidal neurons. Stress impairs working memory via high levels of dopamine D1 receptor (D1R) activation of cyclic adenosine monopho...

Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional an...

This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within...

Attention-Deficit Hyperactivity Disorder (ADHD) is a chronic neurobehavioral disorder characterized by persistent and often acute distractibility, hyperactivity, and impulsivity. It is a condition usually associated with children but in recent years the diagnosis of ADHD in adults has risen significantly. ADHD often coexists with a wide array of ot...

Significance This study of the monkey cerebral cortex revealed age-related changes that help to answer key questions about Alzheimer’s disease (AD): ( i ) why advancing age is the highest risk factor for AD and ( ii ) why neurofibrillary tangles (NFTs) in AD selectively target extensively interconnected pyramidal neurons in the highly evolved assoc...

The working memory circuits of the primate dorsolateral prefrontal cortex (dlPFC) are modulated in a unique manner, often opposite to the molecular mechanisms needed for long-term memory consolidation. Working memory, our "mental sketch pad" is an ephemeral process, whereby transient, mental representations form the foundation for abstract thought....

Disrupted in schizophrenia 1 (DISC1) is a protein implicated in schizophrenia, bipolar disorder, major depressive disorder, and autism. To date, most of research examining DISC1 function has focused on its role in neurodevelopment, despite its presence throughout life. DISC1 also regulates cyclic adenosine monophosphate (cAMP) signaling by increasi...

Background Disrupted in Schizophrenia 1 (DISC1) is a protein implicated in schizophrenia, bipolar disorder, major depressive disorder, and autism. To date, most of research examining DISC1 function has focused on its role in neurodevelopment, despite its presence throughout life. DISC1 also regulate cAMP signaling by increasing PDE4 catabolism of c...

Recent genetic studies have linked mental illness to alterations in disrupted in schizophrenia 1 (DISC1), a multifunctional scaffolding protein that regulates cyclic adenosine monophosphate (cAMP) signaling via interactions with phosphodiesterase 4 (PDE4). High levels of cAMP during stress exposure impair function of the prefrontal cortex (PFC), a...

Patricia S. Goldman-Rakic (1937-2003) transformed the study of the prefrontal cortex (PFC) and the neural basis of mental representation, the basic building block of abstract thought. Her pioneering research first identified the dorsolateral PFC (dlPFC) region essential for spatial working memory, and the extensive circuits of spatial cognition. Sh...

The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in α7 nicotinic acetylcholine receptors (α7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impai...

Neurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate...

Pseudobase benzo[c]phenanthridines and the pharmaceutically acceptable salts thereof of Formula I are provided herein. The variables R, R1, R2, R3, and R4 are defined herein. Certain pseudobase benzo[c]phenanthridines provided herein act as prodrugs, targeting the parent benzo[c]phenanthridinium alkaloid to hydrophilic or hydrophobic regions in th...

The medial prefrontal cortex (mPFC) plays a key role in behavioral variability, action monitoring, and inhibitory control. The functional role of mPFC may change over the lifespan due to a number of aging-related issues, including dendritic regression, increased cAMP signaling, and reductions in the efficacy of neuromodulators to influence mPFC pro...

Motivated, goal-directed behavior requires the coordination of multiple behavioral processes that facilitate interacting with the environment, including arousal, motivation, and executive function. Psychostimulants exert potent modulatory influences on these processes, providing a useful tool for understanding the neurobiology of motivated behavior...

This review describes unique neuromodulatory influences on working memory prefrontal cortical (PFC) circuits that coordinate cognitive strength with arousal state. Working memory arises from recurrent excitation within layer III PFC pyramidal cell NMDA circuits, which are afflicted in aging and schizophrenia. Neuromodulators rapidly and flexibly al...

Schizophrenia associates with impaired prefrontal cortical (PFC) function and alterations in cyclic AMP (cAMP) signaling pathways. These include genetic insults to disrupted-in-schizophrenia (DISC1) and phosphodiesterases (PDE4s) regulating cAMP hydrolysis, and increased dopamine D1 receptor (D1R) expression that elevates cAMP. We used immunoelectr...

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing...

Neural circuits responsible for conscious self-control are highly vulnerable to even mild stress. When they shut down, primal impulses go unchecked and mental paralysis sets in

Neural correlates of aging in the medial prefrontal cortex (mPFC) were studied using an operant delayed response task. The task used blocks of trials with memory-guided (delayed alternation) and visually-guided (stimulus-response) responding. Older rats (24 months) performed at a slow pace compared with younger rats (6 months). They wasted time eng...

The prefrontal cortex (PFC) is among the most evolved brain regions, contributing to our highest order cognitive abilities. It regulates behavior, thought, and emotion using working memory. Many cognitive disorders involve impairments of the PFC. A century of discoveries at Yale Medical School has revealed the neurobiology of PFC cognitive function...

Attention deficit hyperactivity disorder (ADHD), first described by Still in 1902, is a behavioral syndrome associated with attentional deficits, hyperactivity, and impulsivity. Initially viewed as a childhood disorder, ADHD is now known to occur in adults, with a sizeable proportion of adult ADHD reflecting a continuance of the disorder from child...

Subjective values of actions are influenced by the uncertainty and immediacy of expected rewards. Multiple brain areas, including the prefrontal cortex and basal ganglia, are implicated in selecting actions according to their subjective values. Alterations in these neural circuits, therefore, might contribute to symptoms of impulsive choice behavio...

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through exc...

The symptoms of attention-deficit/hyperactivity disorder (ADHD) involve impairments in prefrontal cortical top-down regulation of attention and behavior. All current pharmacological treatments for ADHD facilitate catecholamine transmission, and basic research suggests that these compounds have prominent actions in the prefrontal cortex (PFC). The d...

Dysfunction of the prefrontal cortex (PFC) is a central feature of many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), schizophrenia, and bipolar disorder. Thus, understanding molecular influences on PFC function through basic research in animals is essential to rational drug de...

The primary symptoms of attention deficit/hyperactivity disorder (ADHD) include poor impulse control and impaired regulation of attention. Research has shown that the prefrontal cortex (PFC) is essential for the "top-down" regulation of attention, behavior, and emotion, and that this brain region is underactive in many patients with ADHD. The PFC i...

The symptoms of schizophrenia involve profound dysfunction of the prefrontal cortex (PFC). PFC networks create our "mental sketch pad", and PFC dysfunction contributes to symptoms such as cognitive deficits, thought disorder, delusions and hallucinations. Neuropathological studies of schizophrenia have shown marked loss of dendritic spines in deep...

This study examined the effects of the attention-deficit/hyperactivity disorder treatments, methylphenidate (MPH) and atomoxetine (ATM), on prefrontal cortex (PFC) function in monkeys and explored the receptor mechanisms underlying enhancement of PFC function at the behavioral and cellular levels. Monkeys performed a working memory task after admin...

Neuropsychiatric disorders involve dysfunction of the prefrontal cortex (PFC), a highly evolved brain region that mediates executive functioning. The dorsolateral PFC is specialized for regulating attention and behavior, while the ventromedial PFC is specialized for regulating emotion. These abilities arise from PFC pyramidal cell networks that exc...

Prefrontal cortical (PFC) working memory functions depend on pyramidal cell networks that interconnect on dendritic spines. Recent research has revealed that the strength of PFC network connections can be rapidly and reversibly increased or decreased by molecular signaling events within slender, elongated spines: a process we term Dynamic Network C...

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neuropsychiatric disorder characterized by cardinal features of inattention, locomotor hyperactivity, and poor impulse control. Research indicates that ADHD is associated with alterations in the higher cortical circuits that mediate attention and behavioral control. Given t...

The discovery of dopamine in 1957-8 was one of the seminal events in the development of modern neuroscience, and has been extremely important for the development of modern therapies of neurological and psychiatric disorders. Dopamine has a fundamental role in almost all aspects of behavior — from motor control to mood regulation, cognition and addi...

Schizophrenia is a disorder of the association cortices, with especially prominent structural and functional deficiencies in the dorsolateral prefrontal cortex (PFC). True dorsolateral PFC is found only in higher primates, and is characterized by highly elaborate pyramidal cells with extensive recurrent connections. The development of the primate P...

The prefrontal cortex r regulates behavior, cognition, and emotion by using working memory. Prefrontal functions are impaired by stress exposure. Acute, stress-induced deficits arise from excessive protein kinase C (PKC) signaling, which diminishes prefrontal neuronal firing. Chronic stress additionally produces architectural changes, reducing dend...

Recent advances in neurobiology have aided our understanding of attention-deficit hyperactivity disorder (ADHD). The higher-order association cortices in the temporal and parietal lobes and prefrontal cortex (PFC) interconnect to mediate aspects of attention. The parietal association cortices are important for orienting attentional resources in tim...

The prefrontal cortex (PFC) - the most evolved brain region - subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonge...

Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and locomotor hyperactivity. Recent advances in neurobiology, imaging, and genetics have led to a greater understanding of the etiology and treatment of ADHD. Studies have found that ADHD is associated with weaker function and structure of pref...

Regulator of G protein signaling 4 (RGS4) regulates intracellular signaling via G proteins and is markedly reduced in the prefrontal cortex (PFC) of patients with schizophrenia. Characterizing the expression of RGS4 within individual neuronal compartments is thus key to understanding its actions on individual G protein-coupled receptors (GPCRs). He...

We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and sh...

In schizophrenia, genetic predisposition has been linked to chromosome 22q11 and myelin-specific genes are misexpressed in schizophrenia. Nogo-66 receptor 1 (NGR or RTN4R) has been considered to be a 22q11 candidate gene for schizophrenia susceptibility because it encodes an axonal protein that mediates myelin inhibition of axonal sprouting. Confir...

Understanding effects of estrogen on the medial prefrontal cortex (PFC) may help to elucidate the increased prevalence of depression and post-traumatic stress disorder in women of ovarian cycling age. Estrogen replacement in ovariectomized (OVX) young rats amplifies the detrimental effects of stress on working memory (a PFC-mediated task), but the...

This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNT...

Background: Bipolar disorder and schizophrenia are associated with profound dysfunction of the prefrontal cortex (PFC), with bipolar disorder most associated with changes in ventromedial PFC and schizophrenia more associated with changes in dorsolateral PFC. Discussion: Recent genetic and biochemical studies have also linked these illnesses to d...

The decline in motor performance that accompanies advanced age has unclear neurobiological substrates but may relate, in part, to degeneration of the nigrostriatal dopamine system. This research tested the hypothesis that striatal dopamine transporter (DAT) availability in healthy elderly individuals was related to measures of motor performance. Th...

Previous studies using a mixed beta1 and beta2 adrenergic antagonist, propanolol, have indicated that beta adrenoceptors have little effect on the cognitive functioning of the prefrontal cortex. However, recent studies have suggested that endogenous stimulation of beta1 adrenoceptors impairs working memory in both rats and monkeys. Since propanolol...

Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP3-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP3 receptor (IP3R)-evoked calcium release results in...

The symptoms of mental illness often involve weakened regulation of thought, emotion, and behavior by the prefrontal cortex. Exposure to stress exacerbates symptoms of mental illness and causes marked prefrontal cortical dysfunction. Studies in animals have revealed the intracellular signaling pathways activated by stress exposure that induce profo...

Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research in animals, in combination with observations of patients with cortical lesions, has shown that the PFC is critical for the regulation...

Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment and compromised integrity of neuronal dendrites. Although protein kinase C (PKC) is implicated in structural plasticity, and overactivation of PKC results in working memory impairments in young animals, the role of PKC in prefrontal cortical impairme...

Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal l...

Recent developments in the field of neuroscience have illuminated the understanding of the neural circuits impaired in attention-deficit/hyperactivity disorder (ADHD) and the mechanism of action of treatments used to treat this condition. There is an exciting confluence between emerging studies in basic neurobiology and the genetic, neuroimaging, a...

Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to guide behavior based on representational knowledge of spatial position. It is maintained by spatially tuned, recurrent excitation within networks of prefrontal cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of postsynaptic alpha2A adrenoce...

Norepinephrine (NE) has widespread projections throughout the brain, and thus, is ideally positioned to orchestrate neural functions based on arousal state. For example, NE can increase "signal/noise" ratio in the processing of sensory stimuli, and can enhance long-term memory consolidation in the amygdala and hippocampus through actions at alpha-1...

Dopamine (DA) D1 receptor (D1R) stimulation in prefrontal cortex (PFC) produces an 'inverted-U' dose-response, whereby either too little or too much D1R stimulation impairs spatial working memory. This response has been observed across species, including genetic linkages with human cognitive abilities, PFC activation states and DA synthesis. The ce...

Stimulants such as methylphenidate and amphetamine are currently the most common treatment for attention deficit hyperactivity disorder (ADHD). For years, it was assumed that stimulants had paradoxical calming effects in ADHD patients, whereas stimulating 'normal' individuals and producing locomotor activation in rats. It is now known that low dose...

Low doses of psychostimulants, such as methylphenidate (MPH), are widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Surprisingly little is known about the neural mechanisms that underlie the behavioral/cognitive actions of these drugs. The prefrontal cortex (PFC) is implicated in ADHD. Moreover, dopamine (DA) and nore...

It is well documented that exposure to stress can precipitate or exacerbate many mental illnesses,1,2 including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Women are twice as likely as men to develop these disorders,34 as well as most anxiety disorders and phobias,5 but the biological causes of this discrepancy are po...

The working-memory functions of the prefrontal cortex (PFC) are improved by stimulation of postsynaptic, alpha2A-adrenoceptors, especially in aged animals with PFC cognitive deficits. Thus, the alpha2A-adrenoceptor agonist, guanfacine, greatly improves working-memory performance in monkeys and rats following systemic administration or intra-PFC inf...

Drouin et al. (this issue of J. Neurophysiol. p. 622–632) provide the first analysis of the neurochemical and neurophysiological effects of the stimulant medication, methylphenidate (MPH), in sensory cortex of freely behaving animals. MPH has been prescribed to children and adults with Attention

Neuropsychological and imaging studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research in animals, in combination with observations of patients with cortical lesions, has shown that the PFC is critical for the regulatio...

Restraint stress has been shown to elicit numerous effects on hippocampal function and neuronal morphology, as well as to induce dendritic remodeling in the prefrontal cortex (PFC). However, the effects of acute restraint stress on PFC cognitive function have not been investigated, despite substantial evidence that the PFC malfunctions in many stre...

Previous studies have indicated that beta adrenergic receptor stimulation has no effect on the cognitive functioning of the prefrontal cortex (PFC). Blockade of beta-1 and beta-2 receptors in the PFC with the mixed beta-1/beta-2 antagonist, propanolol, had no effect on spatial working memory performance. However, more selective blockade of beta-1 o...

It is noted that α2-adrenoceptor agonist, guanfacine, is currently in use for the treatment of attention deficit-hyperactivity disorder (ADHD) and for Tourette's syndrome. Tourette's patients activate the prefrontal cortex (PFC) when they successfully inhibit their tics. The use of guanfacine to treat these disorders arose from research in animals,...

The prefrontal cortex guides behaviors, thoughts, and feelings using representational knowledge, i.e., working memory. These fundamental cognitive abilities subserve the so-called executive functions: the ability to inhibit inappropriate behaviors and thoughts, regulate our attention, monitor our actions, and plan and organize for the future. Neuro...

cAMP-dependent protein kinase A (PKA) signaling has a key role in memory processes and has been identified as a potential therapeutic target for memory disorders. The activation of PKA signaling is crucial for the consolidation of long-term memories dependent on the hippocampus and/or the amygdala, By contrast, initial studies indicate that cAMP-PK...

Stimulation of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the prefrontal cortex (PFC) has a beneficial effect on working memory and attentional regulation in monkeys. alpha(2)-adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for the treatment of attention deficit and hyperactivity disorder (ADHD)....

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal c...

Exposure to even mild uncontrollable stress impairs the cognitive functioning of the prefrontal cortex, a brain region critical for insight, judgment, and the inhibition of inappropriate behaviors. Several neurobiological factors may contribute to an exaggeration of the stress response in adolescence, for example, an increased dopaminergic projecti...

The cognitive functions of the prefrontal cortex (PFC) are profoundly impaired in schizophrenic patients. Although dopamine has been the major focus of schizophrenia research, norepinephrine (NE) also has marked influences on PFC cognitive functioning. This review aims to identify the adrenergic receptors which may be appropriate targets for therap...

Many anxiety disorders, as well as major depressive disorder (MDD), are at least twice as prevalent in women as in men, but the neurobiological basis of this discrepancy has not been well studied. MDD is often precipitated by exposure to uncontrollable stress, and is frequently characterized by abnormal or disrupted prefrontal cortex (PFC) function...

Activation of the cAMP/protein kinase A (PKA) pathway has been proposed as a mechanism for improving age-related cognitive deficits based on studies of hippocampal function. However, normal aging also afflicts prefrontal cortical cognitive functioning. Here, we report that agents that increase PKA activity impair rather than improve prefrontal cort...

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Dopamine D1 receptors have critical neuromodulatory influences on the working memory functions of the prefrontal cortex, a brain region affected in many neuropsychiatric disorders. When D1 receptor agents are administered to rats or monkeys performing working memory tasks, an "inverted U" dose/response function is typically observed, whereby either...

Norepinephrine strengthens the working memory, behavioral inhibition, and attentional functions of the prefrontal cortex through actions at postsynaptic alpha2-adrenoceptors (alpha2-AR). The alpha2-AR agonist guanfacine enhances prefrontal cortical functions in rats, monkeys, and human beings and ameliorates prefrontal cortical deficits in patients...

The cognitive functions of the prefrontal cortex (PFC), which include use of working memory to guide behavioral responses and the contents of attentional focus, the inhibition of inappropriate responses, and planning for the future, are among the most fragile in our behavioral repetoire. Deficits in PFC function are evident in every neuropsychiatri...

alpha-2 Noradrenergic agonists improve spatial working memory in animals and in humans. Of the three alpha-2 receptor subtypes, evidence has suggested that this cognitive improvement may be mediated by the alpha-2A receptor subtype, but this has not been established. alpha-2 Agonists are also known to decrease blood pressure significantly. Recent e...

Abstract Rationale. α-2 Noradrenergic agonists improve spatial working memory in animals and in humans. Of the three α-2 receptor subtypes, evidence has suggested that this cognitive improvement may be mediated by the α-2A receptor subtype, but this has not been established. α-2 Agonists are also known to decrease blood pressure significantly. Rec...

This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 week...