Effects of selective catechol-O-methyltransferase inhibitors on single-trial passive avoidance retention in male rats

Khromova, I. V.; Воронина, Т. А.; Kraineva, V. A.; Zolotov, N. N.; Männistö, Pekka T.

doi:10.1016/s0166-4328(96)02242-5

Cited by 28 publications

(12 citation statements)

References 52 publications

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“…The COMT inhibitor tolcapone has been found to yield improvements in lesion-or drug-induced deficits of memory and working memory in rats (Khromova et al, 1995(Khromova et al, , 1997Liljequist et al, 1997) and to yield wideranging cognitive improvements in patients with Parkinson's disease (Gasparini et al, 1997). These findings can be seen as a product of enhancing tonic DA in cases where its availability was limited by experiment or disease.…”

Section: Met Polymorphism Neurocognitive Functionsmentioning

confidence: 99%

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

Bilder

Volavka

Lachman

et al. 2004

Neuropsychopharmacol

717

654

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Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val158 Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D1 transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or detrimental depending on the phenotype, a range of endogenous factors, and environmental exigencies. The literature on phenotypic associations of the COMT Val 158 Met polymorphism is reviewed, highlighting areas where this hypothesis may have explanatory value, and pointing to possible directions for refinement of relevant phenotypes and experimental evaluation of this hypothesis.

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Section: Met Polymorphism Neurocognitive Functionsmentioning

confidence: 99%

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

Bilder

Volavka

Lachman

et al. 2004

Neuropsychopharmacol

717

654

View full text Add to dashboard Cite

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“…Tolcapone, a selective, brain-penetrant COMT inhibitor (Zürcher et al, 1990;Ceravolo et al, 2002), provides a pharmacological way to achieve this goal. Indeed, preliminary data suggest that tolcapone improves memory performance (Gaspirini et al, 1997;Khromova et al, 1997, Liljequist et al, 1997. These data are inconclusive, however, and there has been no evaluation of the effects of tolcapone on PFC catecholamines or in rodent tasks more formally similar to those used to assess human PFC function (e.g., WCST).…”

Section: Introductionmentioning

confidence: 99%

Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat Prefrontal Cortex

Tunbridge

Bannerman²,

Sharp³

et al. 2004

Journal of Neuroscience

384

309

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The Val 158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene affects activity of the enzyme and influences performance and efficiency of the prefrontal cortex (PFC); however, although catecholaminergic neurotransmission is implicated, the underlying mechanisms remain elusive because studies of the role of COMT in PFC function are sparse. This study investigated the effect of tolcapone, a brain-penetrant COMT inhibitor, on a rat model of attentional set shifting, which is dependent on catecholamines and the medial PFC (mPFC). Additionally, we investigated the effect of tolcapone on extracellular catecholamines in the mPFC using microdialysis in awake rats. Tolcapone significantly and specifically improved extradimensional (ED) set shifting. Tolcapone did not affect basal extracellular catecholamines, but significantly potentiated the increase in extracellular dopamine (DA) elicited by either local administration of the depolarizing agent potassium chloride or systemic administration of the antipsychotic agent clozapine. Although extracellular norepinephrine (NE) was also elevated by local depolarization and clozapine, the increase was not enhanced by tolcapone.We conclude that COMT activity specifically affects ED set shifting and is a significant modulator of mPFC DA but not NE under conditions of increased catecholaminergic transmission. These data suggest that the links between COMT activity and PFC function can be modeled in rats and may be specifically mediated by DA. The interaction between clozapine and tolcapone may have implications for the treatment of schizophrenia.

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“…Heterozygous COMT-deficient male mice further exhibit increased aggressive behavior (Gogos et al, 1998), and the more aggressive inbred strains had lower COMT expression levels in the hippocampus relative to the less aggressive strains (Fernandes et al, 2004). Furthermore, the COMT inhibitor tolcapone has been found to yield improvements in lesion-or drug-induced deficits of memory in rats (Khromova et al, 1995(Khromova et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

Significant Association of Catechol-O-Methyltransferase (COMT) Haplotypes with Nicotine Dependence in Male and Female Smokers of Two Ethnic Populations

Beuten

Payne

Jennie

et al. 2005

Neuropsychopharmacol

136

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The catechol-O-methyltransferase (COMT) gene plays a prominent role in dopaminergic circuits central to drug reward. Allelic variants within the COMT gene are therefore potential candidates for examining interindividual differences in vulnerability to nicotine dependence (ND). We analyzed five single nucleotide polymorphisms (SNPs), including the Val/Met variant (rs4680), which results in a three-to fourfold difference in enzyme activity within COMT, for association with the three ND measures, SQ, HSI, and FTND, in 602 nuclear families of African-American (AA) or European-American (EA) origin. The Val/Met variant showed a significant association with the three ND measures in the pooled and EA samples and with FTND in the AA sample. Haplotype analysis revealed a major protective A-G-T haplotype (frequency 23.6%) for rs740603-rs4680-rs174699 in the AA sample (minimum Z ¼ À3.35; P ¼ 0.0005 for FTND), a major protective T-G-T haplotype (frequency 15.2%; minimum Z ¼ À2.92; P ¼ 0.003 for FTND) in the EA sample, and a high-risk C-A-T haplotype (frequency 16.9%; minimum Z ¼ 3.16; P ¼ 0.002 for SQ) in the AA sample for rs933271-rs4680-rs174699. Furthermore, we found that the significant haplotypes within COMT were gender-specific and the significantly associated A-G-T is protective in AA females only, whereas T-G-T is protective in EA males only. Moreover, we found a major high-risk T-A-T haplotype (frequency 56.7%) that showed significant association with the three ND measures in EA males. Further examination of two protective haplotypes, A-G-T in AAs and T-G-T in EAs, indicated that the low COMT enzyme activity Met allele is protective to become nicotine dependent. In summary, our results provide evidence for a role of COMT in the susceptibility to ND and further confirm that its effect is ethnic and gender specific.

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Effects of selective catechol-O-methyltransferase inhibitors on single-trial passive avoidance retention in male rats

Cited by 28 publications

References 52 publications

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

Catechol-O-Methyltransferase Inhibition Improves Set-Shifting Performance and Elevates Stimulated Dopamine Release in the Rat Prefrontal Cortex

Significant Association of Catechol-O-Methyltransferase (COMT) Haplotypes with Nicotine Dependence in Male and Female Smokers of Two Ethnic Populations

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