Abstract
Rationale
The effect of manipulation of the serotonin (5-HT) system on conditioned gaping (presumably reflective of nausea in rats) was evaluated.
Objective
The potential of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (which produces nausea in the clinic), to produce conditioned gaping in rats and of the 5-HT3 antagonists (ondansetron and palonosetron) and the 5-HT1A autoreceptor agonist (8-OH-DPAT) to reverse this effect were evaluated.
Materials and methods
In each of four experiments, rats received three pairings of intraorally delivered 17% sucrose solution and fluoxetine (0, 2, 10 or 20 mg/kg) and 72 h later were given a drug-free test trial. In experiment 2, rats were pretreated with the 5-HT3 antagonists, ondansetron (0, 0.1 or 1.0 mg/kg) or the longer acting palonosetron (0.1 mg/kg), 30 min before each of three sucrose–fluoxetine (20 mg/kg) pairings. In experiment 3, rats were injected with palonosetron (0.1 mg/kg) 2 h before each of three sucrose–fluoxetine (20 mg/kg) or sucrose–lithium chloride (LiCl, 25 mg/kg) pairings. In experiment 4, rats were pretreated with the 5-HT1A autoreceptor agonist, 8-OH-DPAT (DPAT, 0.1 mg/kg) 30 min before each of three sucrose–fluoxetine (20 mg/kg) pairings.
Results
After two sucrose–fluoxetine pairings, the highest dose of fluoxetine tested (20 mg/kg) produced conditioned gaping reactions. These conditioned gaping reactions were prevented by pretreatment with DPAT, but not with the 5-HT3 antagonists. On the other hand, palonosetron administered 2 h prior to sucrose–LiCl pairings attenuated conditioned gaping reactions.
Conclusions
These results suggest that the conditioned nausea produced by SSRIs, but not LiCl, may be resistant to treatment with 5-HT3 antagonists, but not 5-HT1A autoreceptor agonists.
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References
Andrews PLR, Horn CC (2006) Signals for nausea and emesis: implications for models of upper gastrointestinal diseases. Auton Neurosci 125:100–115
Artigas F, Perez V, Alvarez E (1994) Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Arc Gen Psychiatry 51:248–251
Bailey JE, Potokar JP, Coupland NJ, Nutt DJ (1995) The 5HT3 antagonist ondansetron reduces gastrointestinal side effects induced by a specific serotonin re-uptake inhibitor in man. J Psychopharmacol 9:137–141
Bel N, Artigas F (1993) Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei. Synapse 15:243–245
Blundell JE (1984) Serotonin manipulations and the structure of feeding behaviour. Appetite 7:39–56
Brambilla P, Cipriani A, Hotopf M, Barbui C (2005) Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data. Pharmacopsychiatry 38:69–77
Breslin PA, Spector AC, Grill HJ (1992) A quantitative comparison of taste reactivity behaviors to sucrose before and after lithium chloride pairings: a unidimensional account of palatability. Behav Neurosci 106:820–836
Davidson C, Stamford JA (1995) The effect of paroxetine on 5-HT efflux in the rat dorsal raphe nucleus is potentiated by both 5-HT1A and 5-HT1B/D receptor antagonists. Neurosci Lett 188:41–44
Freeman SL, Glatzle J, Robin CS, Valdellon M, Sternini C, Sharp JW, Raybould HE (2006) Ligand-induced 5-HT3 receptor internalization in enteric neurons in the rat ileum. Gastroenterology 131:97–107
Garcia J, Hankins WG, Rusiniak KW (1974) Behavioral regulation of the milieu interne in man and rat. Science 185:824–831
Grill HC, Norgren R (1978) The taste reactivity test. I: mimetic responses to gustatory stimuli in neurologically normal rats. Brain Res 143:263–279
Hjorth S (1993) Serotonin 5-HT1A autoreceptor blockade potentiates the ability of the 5-HT re-uptake inhibitor citalopram to increase nerve terminal output of 5-HT in vivo: a microdialysis study. J Neurochem 60:776–779
Ivernizzi R, Belli S, Samanin R (1992) Citalopram’s ability to increase the extracellular concentration of serotonin in the dorsal raphe prevents the drug’s action in the frontal cortex. Brain Res 584:321–326
Koriech OM (1995) Fluoxetine treatment compromises the antiemetic efficacy of ondansetron in cancer patients. Clin Oncol 7:371–372
Limebeer CL, Parker LA (2000) Ondansetron interferes with lithium-induced conditioned rejection reactions, but not lithium-induced taste avoidance. J Exp Psychol: Anim Behav Process 26:371–384
Limebeer CL, Parker LA (2003) The 5HT1A agonist 8-OH-DPAT dose-dependently interferes with the establishment and expression of lithium-induced conditioned rejection reactions in rats. Psychopharmacology 166:120–126
Limebeer CL, Parker LA, Fletcher PJ (2004) 5,7-Dihydroxytryptamine lesions of the dorsal and median raphe nuclei interfere with lithium-induced conditioned gaping, but not conditioned taste avoidance, in rats. Behav Neurosci 118:1391–1399
Parker LA (1988) Positively reinforcing drugs may produce a different kind of CTA than drugs which are not positively reinforcing. Learn Motiv 19:207–220
Parker LA (1995) Rewarding drugs produce taste avoidance, but not taste aversion. Neurosci Biobehav Rev 19:143–151
Parker LA (2003) Taste avoidance and taste aversion: evidence for two different processes. Learn Behav 31:165–172
Parker LA, Limebeer CL, Kwiatkowska M (2005) Cannabinoids: effects on vomiting and nausea in animal models. In: Mechoulam R (ed) Cannabinoids as therapeutics. Birkhauser, Basel, Switzerland, pp 183–200
Parker LA, Limebeer CL, Rana SA (2009) Conditioned disgust, but not conditioned taste avoidance may reflect conditioned nausea in rats. In: Reilly S, Schachtman T (eds) Conditioned taste aversions: behavioral and neural processes. Oxford University Press, Oxford
Petr Z, Jiri K, Karel V (2006) Serotonin and dopamine in the parabrachial nucleus of rats during conditioned taste aversion learning. Behav Brain Res 170:271–276
Ramamoorthy R, Radhakrishnan M, Borah M (2008) Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: an investigation in behaviour-based rodent models. Behav Pharmacol 19:29–40
Redrobe JP, Bourin M (1997) Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test. Eur J Pharmacol 325:129–135
Reicher MA, Holman EW (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Anim Learn Behav 5:343–346
Travers JB, Norgren R (1986) Electromyographic analysis of the ingestion and rejection of sapid stimuli in the rat. Behav Neurosci 100:544–555
Treiser SL, Cascio CS, O’Donohue TL, Thoa NB, Jacobowitz DM, Kellar KJ (1981) Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science 213:1529–1531
Trindade E, Menon D, Topfer LA, Coloma C (1998) Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis. CMAJ 159:1245–1252
West HL, Mark GP, Hoebel BG (1991) Effects of conditioned taste aversion on extracellular serotonin in the lateral hypothalamus and hippocampus of freely moving rats. Brain Res 556:95–100
Wise R, Yokel P, Dewit H (1976) Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Science 191:1273–1275
Acknowledgements
This research was supported by grants-in-aid from the Natural Sciences and Engineering Council and Theravance, Inc to Linda Parker.
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Limebeer, C.L., Litt, D.E. & Parker, L.A. Effect of 5-HT3 antagonists and a 5-HT1A agonist on fluoxetine-induced conditioned gaping reactions in rats. Psychopharmacology 203, 763–770 (2009). https://doi.org/10.1007/s00213-008-1421-3
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DOI: https://doi.org/10.1007/s00213-008-1421-3