THE FUNCTIONAL SENSITIZATION OF SIGMA-RECEPTORS FOLLOWING CHRONIC SELECTIVE SEROTONIN REUPTAKE INHIBITOR TREATMENT

The purpose of the present study was to investigate the potential impa irment of normal motor function following chronic selective serotonin reuptake inhibitor treatment that may result from sensitisation of sig ma receptors. Rats were chronically treated with either sertraline, ci talopram, paroxetine or fluvoxamine and a selective sigma receptor lig and, di-o-tolylguanidine (DTG), for 28 days. All animals then received an acute intra-rubral injection of either DTG or saline. Following th e direct injection of DTG into the red nucleus, rats chronically treat ed with DTG exhibit a maximal behavioural response characterised as a pronounced dystonia. Animals chronically treated with sertraline and c italopram elicited a response similar to that of control animals follo wing the acute DTG challenge, whereas chronic treatment with paroxetin e and fluvoxamine significantly decreased and increased the dystonic r esponse, respectively. Facial spasticity and vacuous chewing movements were associated with, and reflected the extent of, the DTG-induced dy stonia. Changes in regional biogenic amine concentrations were also de termined. The concentrations of serotonin and noradrenaline were deter mined in the brain stem and cerebellum following the intra-rubral inje ction of either saline or DTG in animals that had been chronically tre ated with a selective serotonin reuptake inhibitor or DTG. There was a significant increase in serotonin concentration in the brain stem as a result of chronic DTG and fluvoxamine treatments. The increase in se rotonin correlated with the reported potentiation of dystonia in anima ls that received 28 days treatment with these drugs. The potentiation of dystonia following chronic DTG and fluvoxamine treatments suggests that these drugs sensitise the sigma(2) receptors, an effect that does not appear to be shared by citalopram, sertraline or paroxetine. (C) 1998 Elsevier Science B.V.