Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variations in serotonin neurotransmission influence alcohol consumption (AC). Levels of 5-HT and metabolites are low in some brain regions of alcohol preferring rats and in CSF of alcoholics. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled clinical trials, SUI have consistently decreased AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Effects were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI also decreased desire to drink and liking for alcohol, thus suggesting a mechanism for effects. Other drugs acting on the 5-HT system have been tested in humans, but results are difficult to interpret. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased alcohol craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). The therapeutic potentials of these medications are being studied. For example, SUI effects on AC were enhanced by a brief psychosocial intervention. Since SUI decrease urge to drink, they may be suitable pharmacological adjuncts in relapse prevention strategies. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for reducing AC.
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PMID:Clinical pharmacology of serotonin-altering medications for decreasing alcohol consumption. 774 4

In vivo microdialysis was used to analyze the role of dorsal raphe nucleus (DRN) neurons in regulating the sleep-waking cycle. Measurements of extracellular serotonin (5-HT) were made in the DRN of freely moving adult cats before and during microdialysis perfusion of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, in artificial CSF. Behavioral state alterations were measured by simultaneous polygraphic recordings. During waking and artificial CSF perfusion of probes histologically localized to the DRN, extracellular 5-HT was 4 fmol/7.5 micro L dialysate sample. With the addition of 8-OH-DPAT (10 microM in artificial CSF) to the perfusate, 5-HT levels in the same state decreased 50%, to 2 fmol/sample (p < 0.01), presumably through 5-HT1A autoreceptor-mediated inhibition of serotonergic neural activity. Concomitantly, this 8-OH-DPAT perfusion produced a short latency, threefold increase in rapid eye movement (REM) sleep, from 10 to 30% of the total recorded time (p < 0.05), whereas waking was not significantly affected. In contrast, and suggesting DRN specificity, 8-OH-DPAT delivery through a probe in the aqueduct did not increase REM sleep but rather tended to increase waking and decrease slow wave sleep. The data on REM sleep provide the first biochemically validated and direct evidence that suppression of DRN serotonergic activity increases REM sleep, and furnish a key complement to our laboratory's in vitro data indicating that mesopontine cholinergic neurons, a target of DRN projections, are inhibited by 5-HT. The 8-OH-DPAT-induced reduction of DRN 5-HT is consistent with the hypothesis that the concomitant REM sleep disinhibition is mediated by DRN serotonergic projections to mesopontine cholinergic neurons, which other data implicate in REM sleep production.
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PMID:Microdialysis perfusion of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the dorsal raphe nucleus decreases serotonin release and increases rapid eye movement sleep in the freely moving cat. 878 56