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

Pharmacological studies using a canine model of narcolepsy have demonstrated that adrenergic rather than serotonergic or dopaminergic uptake inhibition is the primary mode of action of antidepressants on cataplexy, a pathological manifestation of rapid eye movement (REM) sleep atonia that occurs in narcolepsy. This result is in line with the known involvement of adrenergic systems in the regulation of REM sleep. However, the lack of anticataplectic effects of selective serotonergic compounds was puzzling as serotonergic neurons of the dorsal raphe nuclei are known to decrease activity during the REM sleep in a manner similar to the adrenergic neurons of the locus coeruleus. To further explore the role of serotonergic systems, we tested the effect on canine cataplexy of six 5-HT1A agonists and five 5-HT1A antagonists. Results indicate that 5-HT1A agonists significantly suppress cataplexy in correlation with their in vitro affinities to the canine central 5-HT1A receptors. Anticataplectic effects were, however, accompanied by various behavioral changes, such as flattened body posture, increased panting and agitation. In contrast, the selective 5-HT1A antagonist did not aggravate cataplexy, although a 5-HT1A antagonist was able to block the anticataplectic effect of a 5-HT1A agonist. These results suggest that the anticataplectic effects of 5-HT1A agonists are truly mediated by 5-HT1A receptor stimulation. It is, however, likely that anticataplectic effects occur due to the behavioral side effects rather than the direct involvement of this receptor subtype in the regulation of cataplexy. Further studies are therefore necessary to address the question of whether these 5-HT1A agonists hold promise in the pharmacological treatment of human cataplexy.
 ...
PMID:Effect of 5-HT1A receptor agonists and antagonists on canine cataplexy. 789 29

Using in vivo microdialysis either alone or in combination with extracellular unit recordings, we have examined the effect of serotonergic and nonserotonergic drugs applied to the dorsal raphe nucleus (DRN) on behavioural states in the cat. We found that 8-hydroxy-2-(n-dipropylamino)tetralin hydrobromide (8-OH-DPAT), a selective 5-HT1A receptor agonist, induced a dose-dependent increase in wakefulness (W) and decrease in deep slow-wave sleep (SWS), but had no significant effect on the generation of paradoxical sleep (PS) at concentrations of 5-500 microM. At the highest concentration tested, however, PS occurred directly after W, as in narcolepsy. N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohex anecarboxamide maleate (WAY-100635), a selective 5-HT1A receptor antagonist, had no effect on overall behavioural states at concentrations of 50 or 500 microM. Muscimol, a potent GABAA receptor agonist, had little or no effect at concentrations of 10, 50 or 100 microM, but concentrations of 500 or 1000 microM caused a pronounced increase in W and decrease in SWS without inducing any changes in the amount of PS, although PS episodes occurred as in narcolepsy. Bicuculline, a GABAA receptor antagonist, or kainate, an excitatory amino acid agonist, produced a dose-dependent increase in W and decrease in deep SWS and PS. Extracellular unit recordings combined with microdialysis infusion into the DRN demonstrated that only high concentrations of 8-OH-DPAT or muscimol significantly affect a large population of DRN neurons. Taken together, these findings indicate that DRN serotonergic activity does not play any crucial role in PS generation, but is involved in the regulation of W and SWS as well as in narcolepsy.
 ...
PMID:Role of dorsal raphe neurons in paradoxical sleep generation in the cat: no evidence for a serotonergic mechanism. 1113 8