RGD Reference Report - Modulation of hippocampal dopamine metabolism and hippocampal-dependent cognitive function by catechol-O-methyltransferase inhibition. - Rat Genome Database

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Modulation of hippocampal dopamine metabolism and hippocampal-dependent cognitive function by catechol-O-methyltransferase inhibition.

Authors: Laatikainen, LM  Sharp, T  Bannerman, DM  Harrison, PJ  Tunbridge, EM 
Citation: Laatikainen LM, etal., J Psychopharmacol. 2012 Dec;26(12):1561-8. doi: 10.1177/0269881112454228. Epub 2012 Jul 19.
RGD ID: 8662341
Pubmed: PMID:22815336   (View Abstract at PubMed)
PMCID: PMC3546629   (View Article at PubMed Central)
DOI: DOI:10.1177/0269881112454228   (Journal Full-text)

Catechol-O-methyltransferase (COMT) catabolises the catecholamine neurotransmitters and influences cognitive function. COMT modulates dopamine levels in the prefrontal cortex and its action in this region is generally invoked to explain its effects on cognition. However, its role in other brain regions important for cognitive function remains largely unexplored. Here, we investigated COMT's impact on dopamine metabolism in the hippocampus and hippocampal-dependent behaviour. We examined the acute effects of a centrally-acting COMT inhibitor, tolcapone (30 mg/kg i.p.), on dopamine metabolism in the rat dorsal hippocampus, assessed both in tissue homogenates and extracellularly, using in vivo microdialysis. Additionally, we investigated the effect of tolcapone on delayed-rewarded alternation and spatial novelty preference, behavioural tasks which are dependent on the dorsal hippocampus. Tolcapone significantly modulated dopamine metabolism in the dorsal hippocampus, as indexed by the depletion of extracellular homovanillic acid (HVA) and the accumulation of dihydroxyphenylacetic acid (DOPAC). Tolcapone also improved performance on the delayed-rewarded alternation and spatial novelty preference tasks, compared to vehicle-treated rats. Our findings suggest that COMT regulates dorsal hippocampal neurochemistry and modulates hippocampus-dependent behaviours. These findings support the therapeutic candidacy of COMT inhibition as a cognitive enhancer, and suggest that, in addition to the prefrontal cortex, the hippocampus might be a key region for mediating these effects.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
short-term memory  IMP 8662341 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)


Additional Information