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Effects of Pharmacological Manipulation of the Serotonergic/Cholinergic Systems on Sleep Structure in Two 5-HT1A Genotypes: Implications for a Model of Depression

The serotonergic and cholinergic systems are jointly involved in regulating sleep but this balance is theorized to be disturbed in depressed individuals (Janowsky 1972, Jouvet 1972). One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the 5-HT1A receptor predicts an increased risk for depression compared to the wild-type C(-1019) allele.
The goal of this study was to use pharmacological probes in normal controls to model the serotonergic/cholinergic imbalance of depression and its associated abnormalities in sleep structure while controlling for 5-HT1A receptor genotype.
Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles, age 18-27 years were tested on four non-consecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping.
Buspirone suppressed tonic REM: there was a significant increase in REM latency (p<0.001). Galantamine increased tonic REM sleep, leading to more time spent in stage REM (p<0.001) and shorter REM latency (p<0.01). Galantamine and buspirone given together tended to negate the effects of each other on REM sleep measures but disrupted sleep more than either drug alone, showing lower SE and N3% and increased awakenings, Wake% and N1% (p<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition.
These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, and increased sleep fragmentation. The C/G mutation in the 5-HT1A receptor does not appear to cause noticeable differences in the sleep patterns of healthy young females.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/33005
Date January 2015
CreatorsBiard, Kathleen
ContributorsDe Koninck, Joseph
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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