Chronic treatment with fluvoxamine by osmotic minipumps fails to induce persistent functional changes in central 5-HT1A and 5-HT1B receptors, as measured by in vivo microdialysis in dorsal hippocampus of conscious rats
This study investigated the alterations of the 5-HT1A and 5-HT1B autoreceptor function following chronic treatment with fluvoxamine using osmotic minipumps. The 5-HT1A and 5-HT1B autoreceptor function were studied using microdialysis in the dorsal hippocampus. The effect of the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, SC) and the 5-HT1B receptor agonist RU-24969 (100 nM through the dialysis probe for 30 min) on 5-HT release was compared with rats chronically treated with saline. 8-OH-DPAT decreased 5-HT release to 55% and 60% of baseline, while RU-24969 decreased 5-HT release to 66% and 70% of baseline value in the saline and fluvoxamine group, respectively. In both cases, differences between the saline and fluvoxamine groups were not statistically significant. Plasma levels of fluvoxamine after 21 days of treatment ranged from 3 to 5 ng/ml. Fluvoxamine concentration in rat brain during treatment was estimated between 100 and 200 nM, which approximates to the IC50 value of fluvoxamine on the 5-HT transporter in synaptosomes and is 50 times higher than the Kd value for the 5-HT reuptake site. In conclusion, no evidence was found for changes in 5-HT1A,B receptor function using 8-OH-DPAT and RU-24969 as probes after continuous treatment with fluvoxamine by means of osmotic minipumps.
Key wordsMicrodialysis Dorsal hippocampus 5-HT1A and 5-HT1B receptors Chronic treatment Fluvoxamine Rat
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- Bosker FJ, Donker MG, Klompmakers AA, Kurata K, Westenberg HGM (1994) 5-Hydroxytryptamine release in dorsal hippocampus of freely moving rats: modulation by pindolol. Prog Neuro psychopharmacol Biol Psychiatry 18:765–778Google Scholar
- Chaput Y, Blier P, de Montigny C (1988) Acute and long-term effects of antidepressant serotonin (5-HT) reuptake blockers on the efficacy of 5-HT neurotransmission: electrophysiological studies in the rat central nervous system. Adv Biol Psychiatry 17:1–17Google Scholar
- Malagie I, Jacquot C, Gardier AM (1992) In vivo release of scrotonin at fontocortical nerve terminals evoked by electrical stimulation of the dorsal raphe nucleus: effect of repeated administration of fluoxetine. Abstract 2nd International Symposium on Serotonin, Houston, p 47Google Scholar
- Paxinos S, Watson C (1982) The rat brain in stereotoxic coordinates, Academic Press, New YorkGoogle Scholar
- Schechter LE, Bolanos FJ, Gozlan H, Lanfumay L, Haj-Dahmane S, Laporte AM, Fattaccinic, Hamon M (1990) Alterations of central serotonergic and dopaminergic transmission in rats chronically treated with ipsapirone: biochemical and electrophysiological studies. J Pharmacol Exp Ther 255:1335–1347PubMedGoogle Scholar
- Sharp T, Bramwell SR, Hjorth S, Grahame-Smith DG (1989b) Pharmacological characterization of 8-OH-DPAT-induced inhibition of rat hippocampal 5-HT release in vivo as measured by microdialysis. Br J Pharmacol 98:989–997Google Scholar
- Sotelo C, Cholley B, El Mestikawy S, Gozlan H, Harmon M (1990) Direct immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci 12:1144–1154Google Scholar
- Welner SA, de Montigny C, Desorches J, Desjardins P, Suranyi-Cadotte BE (1989) Autoradiographic quantification of serotonin (5-HT1A) receptors following long-term antidepressant treatment. Synapse 4:347–352Google Scholar
- Westenberg HGM, den Boer JA (1993) New findings in the treatment of panic disorder. Pharmacopsychiatry 26:30–33Google Scholar
- Westenberg HGM, den Boer JA (1994) The neuropharmacology of anxiety: a review on the role of serotonin. In: Den Boer JA, Sitsen JM (eds) Handbook of depression and anxiety. Marcel Dekker, New York, pp 405–447Google Scholar