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Abnormal dopaminergic neurotransmission in the hippocampus may be involved in certain aspects of cognitive dysfunction. In the hippocampus, there is little, if any, expression of dopamine transporters (DAT), indicating that the mechanism for dopamine clearance differs from that in the striatum. Here, by means of in-vivo microdialysis in freely moving rats, we tested the hypothesis that the norepinephrine transporter (NET) is involved in dopamine clearance in the hippocampus. We found that systemic administration of the selective NET inhibitor reboxetine (3 mg/kg) and the psychostimulants amphetamine (0.5 mg/kg) and cocaine (10 mg/kg) increased hippocampal dopamine efflux. Local administration of reboxetine (300 μm) produced a large increase in hippocampal dopamine levels that could not be further enhanced by the addition of the NET/DAT inhibitor nomifensine (100 μm). Administration of the specific DAT inhibitor GBR12909 at a concentration (1 mm) that robustly increased dopamine in the nucleus accumbens had a comparably smaller effect in the hippocampus. In line with a minor role of DAT in the hippocampus, we detected very little DAT in this area using ligand binding with radiolabelled RTI-55. Moreover, in contrast to raclopride (100 μm), a dopamine D2-autoreceptor antagonist, local administration of the α2-adrenoceptor antagonist idazoxan (100 μm) increased hippocampal dopamine. Taken together, our data demonstrate an interaction between dopamine and norepinephrine systems in the hippocampus. It is proposed that this interaction originates from a shared uptake mechanism at the NET level.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
This article was published in the following journal.
Name: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychoph
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One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.
A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA1 FIELD and the HIPPOCAMPUS CA3 FIELD.
An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both. It also blocks dopamine receptors.
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