Opioid modulation of gonadotrophin release in tourette's syndrome

Currently the most prevailing hypothesis attempting to explain the pathophysiology of Tourette's syndrome (TS) suggests that the disease results from dopaminergic (DA) hyperactivity (Golden, 1986). Evidence for this hypothesis is indirect and includes the favorable response of these patients to haloperidol, exacerbation of symptoms with dopaminergic drugs (e.g., methylphenidate) and the findings of reduced DA metabolites in the CSF of some TS patients (Singer et al., 1982). We have recently suggested that deranged opioid functions may also be important in the pathophysiology of TS (Sandyk, 1985). Our hypothesis was based on the favorable response of a subgroup of patients to administration of opiate antagonists (e.g., naloxone, naltrexone) (Sandyk et al., 1986), and is also supported by a recent finding demonstrating depletion of striatal dynorphins in a subject with TS (Haber et al., 1986). Furthermore, based on several clinical features of the disease, we have recently suggested that the hypothalamus could be a site of dysfunction in the disease (Sandyk et al., 1986). To investigate the possible role of deranged opioid-mediated hypothalamic functions in TS further, we tested the effects of acute naloxone (Nx) challenge on plasma FSH and LH levels in 5 male TS patients (aged 11-16 years) and in 4 non-TS-diseased controls (narcoleptics). The plasma FSH and LH levels were drawn prior to and 30 min following the intramuscular administration of 1.2 mg of naloxone.