Ethanol Prolongs Clearance of Exogenous Serotonin in the Dorsal Hippocampus but not the Dorsal Raphe Nucleus of Rat Brain
Watch, Janice L.
There is a large body of research connecting dysfunction of serotonergic neurotransmission with alcoholism. The serotonin transporter (SERT) is an important element in the regulation of serotonin (5-HT) neurotransmission by its active uptake of 5-HT from the extracellular fluid (ECF) in order to terminate transmission. SERT function can be downregulated by selective serotonin reuptake inhibitors (SSRIs), thereby increasing extracellular 5-HT. Interestingly, these drugs have been shown to treat certain forms of alcoholism. Additionally, in vivo microdialysis studies have demonstrated that ethanol (EtOH) is able to increase levels of extracellular 5-HT in a similar manner to SSRIs. Few studies, however, have addressed the direct effects of EtOH at the SERT. This may be important, given the recent association between a polymorphism in the human SERT gene and alcoholism. This correlation has prompted us to investigate the possibility of a direct action of EtOH at the SERT. Using high-speed in vivo chronoamperometry, the clearance of locally applied, exogenous 5-HT was measured from the CA3 region of the hippocampus and the dorsal raphe nucleus (DRN) of anesthetized rats following treatment with either EtOH or an SSRI, fluvoxamine. Consistent with our hypothesis, EtOH appears to dose dependently inhibit the clearance of 5-HT from the CA3 region of the rat hippocampus. This effect, however, is not seen in the DRN, suggesting that EtOH differentially affects SERT function in the rat brain. The results of the present study, in conjunction with evidence of differences in expression of the 5-HT1B autoreceptor and the 5-HT3 receptor in the CA3 and the DRN, suggest that rather than a direct action at the SERT, EtOH may instead exert its action on 5-HT clearance via receptor-mediated control of the SERT.
vi, 28 p.
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