INVOLVEMENT OF THE SEROTONIN SYSTEM IN SSRI-INDUCED ANTINOCICEPTION

Serotonin specific reuptake inhibitors (SSRI) may induce antinociception however, the mechanism of this effect is not clear. SSRls increase 5-HT levels in neuronal synapses and facilitate serotonergic activity. In this study, therefore, the activity of para-chlorophenylalanine (pCPA), which reduces 5-HT release, and 5- hydroxy tryptophan (5-HTP), a precursor of 5-HT, were examined on the antinociceptive activity of six SSRls, in the abdominal constriction test. The compounds studied included fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram and zimelidine. The effects of pCPA and 5-HTP were also evaluated on morphine analgesia as a standard compound. All antidepressants tested demonstrated dose-inhibition of acetic acid-induced abdominal constrictions. The antinociceptive activities of morphine, fluoxetine, fluvoxamine and sertraline, but not paroxetine, citalopram and zimelidine were significantly reduced by pCPA. Subsequently, 5- HTP restored the reduced antinociception of morphine, fluoxetine and fluvoxamine caused by pCP A. Furthermore, 5-HTP increased morphine, fluoxetine, fluvoxamine and sertraline-induced antinociception. Opioid receptor antagonists have been shown to reduce the antinociception induced by morphine, fluoxetine, fluvoxamine and sertraline but not by paroxetine, citalopram and zimelidine. It can be concluded, therefore, that the serotonin system is only involved in antinociception produced by antidepressants, and their antinociception is opioid antagonist reversible.