Alpha-2 Adrenergic Modulation of Prefrontal Cortical Neuronal Activity Related to Spatial Working Memory in Monkeys

Li, B

doi:10.1016/s0893-133x(99)00070-6

Cited by 148 publications

(114 citation statements)

References 32 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Given the beneficial effects of clonidine and related a 2 agonists on prefrontal cortical function (Li et al, 1999;Wang et al, 2007) as well as the important role of the prefrontal cortex in the positive actions of a 2 agonists on spatial working memory (Arnsten and Goldman-Rakic, 1985;see Arnsten, 2004 for review), it is likely that if clonidine improves memory in either model, this phenomenon would be linked to enhanced prefrontal cortical function. In the case of animals with hippocampal damage, the enhancement of prefrontal function could act to compensate for the loss of hippocampal modulation of spatial working memory.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Bardgett

Points

Ramsey-Faulkner

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Spatial memory impairments observed in Alzheimer's disease and schizophrenia have been attributed to many factors, including glutamate hypofunction and reduced hippocampal volume. Clonidine, a non-specific a 2 adrenergic receptor agonist, improves spatial memory in animals treated with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine; however, its effects on memory deficits produced by other NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if clonidine could alleviate memory deficits produced by the NMDA antagonist, MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with clonidine (0.01 or 0.05 mg/kg) or saline, and treated with MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing. MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze. Clonidine pretreatment significantly alleviated these druginduced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that clonidine alleviates memory impairments produced by glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for memory disorders not linked to a single pathophysiological mechanism.

show abstract

Section: Introductionmentioning

confidence: 99%

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Bardgett

Points

Ramsey-Faulkner

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

Section: Prefrontal α 2a -Adrenoceptor Stimulation Ameliorates Cognitmentioning

confidence: 99%

“…In this paper, we review research progress in the relevant fi elds, focusing on the potential relationship between prefrontal α 2A -adrenoceptors and ADHD in nonhuman primates [35][36][37][38][39] . including poor attention regulation [40] , limited working memory [41] , and inability to inhibit inappropriate motor activity [42] .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Our work showed that both systemic administration and local infusion of guanfacine into the PFC improve visuomotor associative learning [70,75] . Using an iontophoretic technique, stimulation of α 2A -adrenoceptors in the PFC was found to increase the spiking activity associated with working memory in behaving monkeys [37,76] .Neuronal activity in the PFC associated with working memory can be enhanced by α 2A -adrenoceptor stimulation through cAMP-HCN signaling pathways [76,77] . Our work suggested that under normal physiological conditions, the α 2A -adrenoceptors in pyramidal cells can be activated through Gi-cAMP-HCN signaling [78] .…”

mentioning

confidence: 98%

See 2 more Smart Citations

Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder

Sun

Luo

et al. 2015

Neurosci. Bull.

View full text Add to dashboard Cite

Attention deficit and hyperactivity disorder (ADHD), a prevalent syndrome in children worldwide, is characterized by impulsivity, inappropriate inattention, and/or hyperactivity. It seriously afflicts cognitive development in childhood, and may lead to chronic under-achievement, academic failure, problematic peer relationships, and low self-esteem. There are at least three challenges for the treatment of ADHD. First, the neurobiological bases of its symptoms are still not clear. Second, the commonly prescribed medications, most showing short-term therapeutic efficacy but with a high risk of serious side-effects, are mainly based on a dopamine mechanism. Third, more novel and effi cient animal models, especially in nonhuman primates, are required to accelerate the development of new medications. In this article, we review research progress in the related fi elds, focusing on our previous studies showing that blockade of prefrontal cortical α 2A -adrenoceptors in monkeys produces almost all the typical behavioral symptoms of ADHD.Keywords: prefrontal cortex; α 2A -adrenoceptors; cognitive functions; attention defi cit and hyperactivity disorder; animal models ·Review· IntroductionAttention deficit and hyperactivity disorder (ADHD) is one of the most prevalent childhood neurodevelopmental conditions, affecting 3-5% of grade-school children worldwide [1] . It is characterized by i nappropriate levels of inattention, i mpulsivity, and/or hyperactivity [2][3][4] . These symptoms develop in childhood, and can persist into adolescence and adulthood [5] . ADHD seriously affects cognitive development [6][7][8] , and, without appropriate treatment, has consequences for the risk of anxiety, substance abuse, and depression in adulthood [ 2, 5, 9] .T he neurobiological bases o f ADHD symptoms are still not clear [10] . Clarifying them can help better understand the biological vulnerabilities that may underlie ADHD in a specifi c patient and how to modulate the responses to treatment, thereby contributing to better and more effective therapy.It has been suggested that the symptoms involve a dopaminergic mechanism in the prefrontal cortex (PFC) and striatum [11, 12] . Experimentally decreased dopamine (DA) release in the PFC results in ADHD-like symptoms [13, 14] .To date, DA dysregulation is thought to be central to the neurobiology of ADHD, and its pharmacological treatment, such as m ethylphenidate (MPH, i.e. Ritalin) [15][16][17] , levels the DA c oncentration in the synapse and extrasynaptic space in the PFC as a blocker of the DA transporter. MPH ameliorates inappropriate inattention [18][19][20] , decreases impulsivity [21] , and enhances inhibitory control [22] . However, as MPH is a prescription psychostimulant, there are strong concerns over drug dependence, paranoia, schizophrenia, and behavioral sensitization that might be caused by longterm therapy, similar to other stimulants [23][24][25].Converging evidence indicates that the pathophysiology of ADHD has multiple origins [26][27][28][29][30][31][32] ; for i...

show abstract

Experimental Strategies for Investigating Psychostimulant Drug Actions and Prefrontal Cortical Function in ADHD and Related Attention Disorders

Agster

Clark

Gao

et al. 2011

The Anatomical Record

View full text Add to dashboard Cite

Amphetamine-like psychostimulant drugs have been used for decades to treat a variety of clinical conditions. Methylphenidate (MPH) - RitalinR, a compound that blocks reuptake of synaptically released norepinephrine (NE) and dopamine (DA) in the brain, has been used for more than 30 years in low dose, long-term regimens to treat attention deficit-hyperactive disorder (ADHD) in juveniles, adolescents, and adults. These agents are now also becoming increasingly popular among healthy individuals from all walks of life (e.g. military, students) and age groups (teenagers thru senior citizens) to promote wakefulness and improve attention. While there is agreement regarding the primary biochemical action of MPH, the physiological basis for its efficacy in normal individuals and ADHD patients is lacking. Study of the behavioral and physiological actions of clinically and behaviorally relevant doses of MPH in normal animals provides an opportunity to explore the role of catecholamine transmitters in prefrontal cortical function and attentional processes as they relate to normal operation of brain circuits and ADHD pathology. The goal of ongoing studies has been to: 1) assess the effects of low dose MPH on rodent performance in a well characterized sensory-guided sustained attention task, 2) examine the effects of the same low-dose chronic MPH administration on task-related discharge of prefrontal cortical (PFC) neurons and 3) investigate the effects of NE and DA on membrane response properties and synaptic transmission in identified subsets of PFC neurons. Combinations of these approaches can be used in adolescent, adult and aged animals to identify the parameters of cell and neural circuit function that are regulated by MPH and to establish an overarching explanation of how MPH impacts PFC operations from cellular through behavioral functional domains.

show abstract

Alpha-2 Adrenergic Modulation of Prefrontal Cortical Neuronal Activity Related to Spatial Working Memory in Monkeys

Abstract: The prefrontal cortex (PFC) plays a critical role in regulating spatial working memory (SWM) (Fuster et al.

Cited by 148 publications

References 32 publications

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder

Experimental Strategies for Investigating Psychostimulant Drug Actions and Prefrontal Cortical Function in ADHD and Related Attention Disorders

Contact Info

Product

Resources

About