Dances with black widow spiders: Dysregulation of glutamate signalling enters centre stage in ADHD

Lesch, Klaus‐Peter; Merker, S.; Reif, Andreas; Novák, Miroslav

doi:10.1016/j.euroneuro.2012.07.013

Cited by 60 publications

(46 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glutamate is the major excitatory amino acid neurotransmitter involved in learning and memory (see Riedel et al 2003 for a review) and is considered to play a pivotal role in addiction-like behaviors (Kalivas 2009) and impulse disorders (Lesch et al 2013; Pattij and Vanderschuren 2008). Because memory processes have been proposed to underlie discounting (Killeen 2011), glutamatergic functioning is a potential mechanism underlying sensitivity to delayed and/or uncertain reinforcement.…”

Section: Introductionmentioning

confidence: 99%

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

et al. 2014

View full text Add to dashboard Cite

Rationale Discounting of delayed and probabilistic reinforcement is linked to increased drug use and pathological gambling. Understanding the neurobiology of discounting is important for designing treatments for these disorders. Glutamate is considered to be involved in addiction-like behaviors; however, the role of ionotropic glutamate receptors (iGluRs) in discounting remains unclear. Objectives The current study examined the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor blockade on performance in delay and probability discounting tasks. Methods Following training in either delay or probability discounting, rats (n = 12, each task) received pretreatments of the NMDA receptor antagonists MK-801 (0, 0.01, 0.03, 0.1, or 0.3 mg/kg, s.c.) or ketamine (0, 1.0, 5.0, or 10.0 mg/kg, i.p.), as well as the AMPA receptor antagonist CNQX (0, 1.0, 3.0, or 5.6 mg/kg, i.p.). Hyperbolic discounting functions were used to estimate sensitivity to delayed/probabilistic reinforcement and sensitivity to reinforcer amount. Results An intermediate dose of MK-801 (0.03 mg/kg) decreased sensitivity to both delayed and probabilistic reinforcement. In contrast, ketamine did not affect the rate of discounting in either task but decreased sensitivity to reinforcer amount. CNQX did not alter sensitivity to reinforcer amount or delayed/probabilistic reinforcement. Conclusions These results show that blockade of NMDA receptors, but not AMPA receptors, decreases sensitivity to delayed/probabilistic reinforcement (MK-801) and sensitivity to reinforcer amount (ketamine). The differential effects of MK-801 and ketamine demonstrate that sensitivities to delayed/probabilistic reinforcement and reinforcer amount are pharmacologically dissociable.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In addition, the three members of the family have been detected in several large-scale studies (Ishikawa et al 1997 ;Clark et al 2003 ;Ota et al 2004 ;Gerhard et al 2004 ;Nagase et al 2000a ;Otsuki et al 2005 ;Taylor et al 2006 ;Deloukas et al 2001 ). The proteins have been suggested to be implicated in cirrhosis, lupus, schizophrenia, and ASDs (Lesch et al 2012 ;Anney et al 2010 ;Ahmad et al 2012 ;Shirai et al 2012Shirai et al , 2013.…”

Section: The Flrt Familymentioning

confidence: 99%

“…Furthermore, both LPHN3 and FLRT3 have been identifi ed as risk genes for attention-defi cit/ hyperactivity disorder (ADHD) [reviewed by Lesch et al ( 2012 )]. However, a direct relationship between changes in the function or expression of FLRT3 and these diseases remains to be determined.…”

Section: Diseasesmentioning

confidence: 99%

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

Winther

Walmod

2013

Advances in Neurobiology

View full text Add to dashboard Cite

Leucine-rich repeats (LRRs) are motifs that form protein-ligand interaction domains. There are approximately 140 human genes encoding proteins with extracellular LRRs. These encode cell adhesion molecules (CAMs), proteoglycans, G-protein-coupled receptors, and other types of receptors. Here we give a brief description of 36 proteins with extracellular LRRs that all can be characterized as CAMs or putative CAMs expressed in the nervous system. The proteins are involved in multiple biological processes in the nervous system including the proliferation and survival of cells, neuritogenesis, axon guidance, fasciculation, myelination, and the formation and maintenance of synapses. Moreover, the proteins are functionally implicated in multiple diseases including cancer, hearing impairment, glaucoma, Alzheimer's disease, multiple sclerosis, Parkinson's disease, autism spectrum disorders, schizophrenia, and obsessive-compulsive disorders. Thus, LRR-containing CAMs constitute a large group of proteins of pivotal importance for the development, maintenance, and regeneration of the nervous system.

show abstract

“…The aberrant regulation of neurotransmitters has been implicated in numerous disease states including schizophrenia, Parkinson's disease, Alzheimer's disease, mood disorders, attention-deficit/hyperactivity disorder (ADHD), and drug addiction (Brambilla et al, 2003;Moghaddam and Javitt, 2012;Lesch et al, 2013;Paula-Lima et al, 2013;Poletti and Bonuccelli, 2013;Quintero, 2013). Of particular note, the frontal cortex is a glutamate-rich brain region and deficits in this area cause poor impulse control, distractibility, hyperactivity, forgetfulness and poor organization and planning (Stuss and Levine, 2002).The frontal cortex is organized into different cortical layers, including the cingulate cortex, prelimbic cortex, infralimbic cortex, and the dorsal peduncle.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous glutamate recordings in the frontal cortex network with multisite biomorphic microelectrodes: New tools for ADHD research

Miller

Quintero

Pomerleau

et al. 2015

Journal of Neuroscience Methods

View full text Add to dashboard Cite

Dances with black widow spiders: Dysregulation of glutamate signalling enters centre stage in ADHD

Cited by 60 publications

References 136 publications

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

Neural Cell Adhesion Molecules Belonging to the Family of Leucine-Rich Repeat Proteins

Simultaneous glutamate recordings in the frontal cortex network with multisite biomorphic microelectrodes: New tools for ADHD research

Contact Info

Product

Resources

About