Effects of nicotine on head-shakes and tryptophan metabolites

RATIONALE: Nicotine appears to ameliorate the tics of Tourette syndrome. There is evidence that plasma concentrations of the tryptophan metabolite kynurenine may be elevated in this condition. Rodent head-shakes have been proposed as a putative model of Tourette syndrome and are potentiated by kynurenine. OBJECTIVES: To determine the effects of acute and chronic nicotine on mouse head-shakes, and to study whether nicotine influences brain and plasma levels of kynurenine and certain of its further metabolites in this species. METHODS: Behavioural and biochemical studies. RESULTS: Acute (-10 min) administration of (-)-nicotine, or the nicotinic agonist (+)-epibatidine, dose dependently attenuated head-shakes induced by the 5-HT2A/2C receptor agonist +/-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). This attenuation was inhibited by the nicotinic receptor antagonist mecamylamine. Acute nicotine did not affect either spontaneous head-shakes or plasma and brain kynurenine. Fifteen hours after the last of twice daily injections of nicotine (1.6 mg/kg for 7 days), the frequency of spontaneous and DOI-induced head-shakes was significantly potentiated and there was a significant elevation of both plasma and brain kynurenine, although no differences were detected in plasma concentrations of tryptophan, kynurenic acid, 3-hydroxykynurenine or 3-hydroxyanthranilic acid. Brain levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid were also unaffected. In contrast, all these measures were unchanged 15 h after a single nicotine dose (1.6 mg/kg). CONCLUSIONS: The acute studies indicate that head-shakes induced by DOI are indeed inhibited by nicotinic receptor agonists and suggest that this is not a consequence of an increase in kynurenine. While a role for kynurenine or its metabolites in increasing the head-shake rate after chronic nicotine cannot be excluded, alternative explanations included alterations in the expression or functional status of nicotinic receptor components and further work will be required to characterise this effect.