Axo-Axonic Synapses in the Rat Striatum

Kornhuber, Johannes; Kornhuber, Malte

doi:10.1159/000115598

Cited by 28 publications

(9 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2b) as suggested by Rowlands and Rob erts [21]. The postulated serial synapses have been found morphologically [12], Furthermore, the present findings with chronic haloperidol administration do not contradict data from experiments with single doses of haloperidol: Kim and Hassler [9] found a significant decrease of the GABA levels in both the rat striatum and substantia nigra. It is well known that the acute and chronic clinical effects of neuroleptic treat ment are at least partially different.…”

Section: Discussionsupporting

confidence: 81%

Chronic Haloperidol Administration Enhances the γ-Aminobutyric Acid Level in the Rat Striatum without Altering the Glutamate Level

Kornhuber¹,

Kim²,

Kornhuber³

et al. 1984

Eur Neurol

View full text Add to dashboard Cite

A dose-dependent elevation of striatal γ-aminobutyric acid (GABA) level was found under chronic treatment with haloperidol, a classical neuroleptic drug. The unaltered GABA level in the substantia nigra is compatible with the existence of GABAergic interneu-rons in the striatum, which are inhibited by the afferent dopaminergic innervation to the striatum. The glutamate levels of the cerebrospinal fluid (CSF) and different brain regions investigated were not significantly changed by haloperidol. By contrast, we found in an earlier investigation with sulpiride, an atypical neuroleptic drug, a changed glutamate level in the striatum and the CSF and an unaltered GABA level. These findings may correspond to the different clinical effects of classical and atypical neuroleptics.

show abstract

Section: Discussionsupporting

confidence: 81%

Chronic Haloperidol Administration Enhances the γ-Aminobutyric Acid Level in the Rat Striatum without Altering the Glutamate Level

Kornhuber¹,

Kim²,

Kornhuber³

et al. 1984

Eur Neurol

View full text Add to dashboard Cite

show abstract

“…PFC afferents to the striatum regulate activity of mesocortical dopamine neurons projecting to PFC via GABA neurons, which modulate working memory and executive function that are mediated by PFC (Seamans & Yang, 2004; Winterer & Weinberger, 2004). PFC afferents to the striatum are, in turn, regulated by midbrain dopamine systems as the PFC afferents and dopaminergic neurons terminate on single dendrites of striatal neurons (Freund, Powell, & Smith, 1984; Kornhuber & Kornhuber, 1983). The PFC-striato-thalamo-cortical loop receives regulatory input from the hippocampus that allows the binding of contextual information provided by the hippocampus with behavioral plans provided by PFC to update representations of the external world (Grace et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome

Takarae

Schmidt

Tassone

et al. 2009

Cognitive, Affective, & Behavioral Neuroscience

View full text Add to dashboard Cite

). The q11.2 region of chromosome 22 includes the catechol-O-methyltransferase (COMT) gene, which is critical in metabolizing dopamine by methylation. A common polymorphism involving a valine (VAL) to methionine (MET) substitution at codon 158 in the aminoacid sequence changes the stability of enzyme activity. As a result, the VAL variant produces 40% more enzyme activity than does the MET variant at normal body temperature (Chen et al., 2004). Because the dopamine transporter is much less abundant in prefrontal cortex (PFC) than in the striatum, the synaptic deactivation of dopamine in PFC depends to a much greater degree on COMT. For example, methylation accounts for more than 60% of metabolic degradation of dopamine in frontal cortex in comparison with 15% in the striatum and nucleus accumbens (Karoum, Chrapusta, & Egan, 1994).The observation that variation in a single gene could explain a large amount of variance in dopamine metabolism in PFC is particularly interesting in light of previous reports of a mediating role for dopamine in higher cognitive functions (Kimberg & D'Esposito, 2003). Although it is difficult to accurately measure dopamine levels in the human brain, genotypes for COMT could be used as an indicator of dopamine metabolism. The efficiency of PFC-mediated cognition in typically developing (TD) adults has already been shown to vary by the COMT genotype. A large-sample study by Egan et al. (2001) demonstrated that TD adults with homozygous VAL alleles made more perseverative errors than did those with homozygous MET alleles during the Wisconsin Card Sort Task, and this effect was deemed reliable in a more recent meta-analysis based on 17 published studies (Barnett, Jones, Robbins, & Müller, 2007). Egan et al. also conducted a functional imaging study using an N-back task in which participants were asked to indicate whether the current stimulus was the same as the one presented N trials before. They found that those with homozygous VAL alleles produced greater activation in PFC and in the anterior cingulate-which also receives rich dopaminergic innervation-than did those with homozygous MET alleles. The observed difference in brain activation when the performance level of the two groups was similar suggests less efficient processing in the relevant PFC circuitry in the VAL group. Similar findings were found with different cognitive paradigms that required high demands for cognitive control and attention regulation (Blasi et al., 2005;Winterer et al., 2006).It has been shown that the effect of dopamine levels on cognition follows an inverse U function in which a relatively small range of dopamine optimizes cognitive performance (Williams & Goldman-Rakic, 1995 Dopamine plays a critical role in regulating neural activity in prefrontal cortex (PFC) and modulates cognition via a hypothesized inverse U function. We investigated PFC function in children with chromosome 22q11.2 deletion syndrome (22q11.2DS) in which one copy of catechol-O-methyltransferase (COMT) is deleted, thereby shifting them towa...

show abstract

“…Dopamine is a chemical messenger that can behave as either a neurotransmitter or a neuromodulator in different regions of the central nervous system. Part of the effects of endogenous dopamine involves modulation of glutamate receptor function; this seems to be the case in the neostriatum, where dopamine can be released in close proximity to glutamatergic synapses ( Freund et al ., 1984 ; Kornhuber & Kornhuber, 1983 ), and possibly in other brain regions and in the retina. Both facilitation and inhibition of ionotropic glutamate responses by dopamine have been described, even in the same preparation (e.g., Akaike et al ., 1987 ).…”

Section: Introductionmentioning

confidence: 94%

Direct inhibition of the N‐methyl‐D‐aspartate receptor channel by dopamine and (+)‐SKF38393

Castro

Mello

et al. 1999

British J Pharmacology

View full text Add to dashboard Cite

1 Dopamine is known to modulate glutamatergic synaptic transmission in the retina and in several brain regions by activating speci®c G-protein-coupled receptors. We have examined the possibility of a di erent type of mechanism for this modulation, one involving direct interaction of dopamine with ionotropic glutamate receptors. 2 Ionic currents induced by fast application of N-methyl-D-aspartate (NMDA) were recorded under whole-cell patch-clamp in cultured striatal, thalamic and hippocampal neurons of the rat and in retinal neurons of the chick. Dopamine at concentrations above 100 mM inhibited the NMDA response in all four neuron types, exhibiting an IC 50 of 1.2 mM in hippocampal neurons. The time course of this inhibition was fast, developing in less than 100 ms. 3 The D 1 receptor agonist (+)-SKF38393 mimicked the e ect of dopamine, with an IC 50 of 58.9 mM on the NMDA response, while the enantiomer (7)-SKF38393 was ine ective at 50 mM. However, the D 1 antagonist R(+)-SCH23390 did not prevent the inhibitory e ect of (+)-SKF38393. 4 The degree of inhibition by dopamine and (+)-SKF38393 depended on transmembrane voltage, increasing 2.7 times with a hyperpolarization of about 80 mV. The voltage-dependent block by dopamine was also observed in the presence of MgCl 2 1 mM. 5 Single-channel recordings showed that the open times of NMDA-gated channels were shortened by (+)-SKF38393. 6 These data suggested that the site to which the drugs bound to produce the inhibitory e ect was distinct from the classical D 1 -type dopamine receptor sites, possibly being located inside the NMDA channel pore. It is concluded that dopamine and (+)-SKF38393 are NMDA channel ligands.

show abstract

Axo-Axonic Synapses in the Rat Striatum

Cited by 28 publications

References 16 publications

Chronic Haloperidol Administration Enhances the γ-Aminobutyric Acid Level in the Rat Striatum without Altering the Glutamate Level

Chronic Haloperidol Administration Enhances the γ-Aminobutyric Acid Level in the Rat Striatum without Altering the Glutamate Level

Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome

Direct inhibition of the N‐methyl‐D‐aspartate receptor channel by dopamine and (+)‐SKF38393

Contact Info

Product

Resources

About