The sensitivity of post-synaptic 5-HT2c receptors is not increased in patients with CFS. This suggests that the increased PRL response to fenfluramine in CFS is due to elevated activity of pre-synaptic 5-HT neurones. This change is unlikely to be due to increased peripheral availability of tryptophan.
The 5-HT 2C receptor gene has been localised to the X chromosome and contains a C-G polymorphism at codon 23 (nucleotide 68) such that serine replaces cysteine in the receptor in about 15% of the population (Lappalainen et al. 1995;Sodhi et al. 1995). Sodhi et al (1995) found that patients with schizophrenia who possessed serine alleles of the 5-HT 2C receptor experienced a better therapeutic response to clozapine, an atypical antipsychotic agent which includes 5-HT 2C receptor antagonism among its pharmacological properties. This raises the possibility that the functional consequences of 5-HT 2C blockade may differ between subjects according to their 5-HT 2C receptor genotype. Drugs that antagonise 5-HT 2C receptors produce dose-related increases in slow wave sleep (SWS) in the sleep polysomnogram (EEG) (Sharpley et al. 1990). The aim of the present study was to assess whether the increase in SWS that follows administration of the atypical antipsychotic and 5-HT 2C receptor antagonist, olanzapine (Sharpley et al. 2000), differed in subjects with serine substituted 5-HT 2C receptors.DNA was extracted from buccal swabs or blood samples using standard methods. Genotype was identified using a previously described method using restriction analysis of a 104 bp fragment using the Hsp92II isoschizomer of NlaIII (Burnett et al. 1997). From this procedure we identified two groups of 12 healthy male volunteers, who possessed the cysteine (CYS) (mean age 36.9 years, range 23-57 years) and serine (SER) (mean age 38.5 years, range 21-53 years) substituted 5-HT 2C receptors, respectively. Prior to entry into the study, which was approved by the local ethics committee, subjects underwent medical and psychiatric screening to ensure they had no past or present history of sleep disturbance, psychiatric disorder or significant physical illness, and were free of psychotropic medication for at least 3 months. Subjects were studied on 2 nights, each separated by 7-14 days, and were randomly allocated to receive single oral doses of olanzapine 5 mg and matching placebo, given 4 h before their pre-arranged bedtime in a double-blind, parallel group design.Home based sleep recordings were made using the Oxford Medilog cassette monitoring system. Standard sleep montage electrodes were applied in the Research Unit and the subjects then returned home to sleep as usual. Subjects' sleep routines were kept constant for all study nights and preceding nights. The records were analysed using the Oxford Medilog sleep stager (9200), which provides measures for all aspects of sleep architecture according to standard criteria (Rechtschaffen and Kales 1968). In addition, the tapes were visually inspected and edited by a scorer blind to treatment status. The sleep data were analysed with a two-way repeated measures analysis of variance (ANOVA) with "olanzapine" (olanazapine versus placebo) as a main within-subject factor and "genotype" (CYS versus SER) as the between-subjects factor.The ANOVA showed a significant effect of olanzapine treatment on SWS (m...
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