Is a Divergent Central Serotonergic Activity Responsible for Either Despair or Learning Behavior in Intact Wistar or Sprague-Dawley CD Rats, Respectively? A Concomitant Behavioral and Electrochemical Analysis
Francesco Crespi
DOI: 10.4236/psych.2010.13028   PDF    HTML     6,465 Downloads   12,245 Views   Citations


Behavioral observations combined with electrochemical analysis have been performed in Wistar or Sprague-Dawley CD rats in the attempt to clarify earlier controversial behavioral reports. In particular, these rats were submitted to FST and to repeated Forced Swimming (rFS, during 4 days). In parallel, voltammetric in vivo analysis of serotonin (5-HT) levels in platelet-rich plasma (PRP) collected daily from these animals was also performed as it is known that peripheral 5-HT levels monitored in rat PRP mirror cerebral 5-HT contents. Thus, combined behavioral-voltammetric studies allow deducing changes of central 5-HT levels that could be correlated to FST or rFS, with the advantage of non invasive analysis of central neurotransmitter activities in intact behaving animals. In particular, combined beha-vioral-voltammetric results suggest that “behavioral despair” is the process interesting Wistar rats when submitted to FST or rFS while “learning to be immobile” is the process involving Sprague-Dawley CD rats.

Share and Cite:

Crespi, F. (2010). Is a Divergent Central Serotonergic Activity Responsible for Either Despair or Learning Behavior in Intact Wistar or Sprague-Dawley CD Rats, Respectively? A Concomitant Behavioral and Electrochemical Analysis. Psychology, 1, 209-219. doi: 10.4236/psych.2010.13028.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. D. Porsolt, M. Le Pichon and M. Jalfre, “Depression: A New Animal Model Sensitive to Anti Depressant Treat- ments,” Nature, Vol. 266, No. 5604, 1977, pp. 730-732.
[2] F. Borsini and A. Meli, “Is the Forced Swimming Test a Suitable Model for Revealing Antidepressant Activity?” Psychopharmacology, Vol. 94, No. 2, 1988, pp. 147-160.
[3] T. J. Connor, P. Kelliher, Y. Shen, A. Harkin, J. P. Kelly and B. E. Leonard, “Effect of Subchronic Antidepressant Treatments on Behavioral, Neurochemical, and Endocrine Changes in the Forced-Swim Test,” Pharmacology Bio- chemistry and Behavior, Vol. 65, No. 4, 2000, pp. 591-597.
[4] M. J. Detke and I. Lucki, “Detection of Serotonergic and Noradrenergic Antidepressants in the Rat Forced Swim- ming Test: The Effect of Water Depth,” Behavioural Brain Research, Vol. 73, No. 1-2, 1996, pp. 43-46.
[5] R. D. Porsolt, A. Bertin, N. Blavet, M. Deniel and M. Jalfre, “Immobility Induced by Forced Swimming in Rats: Ef- fects of Agents which Modify Central Catecholamine and Serotonin Activity,” European Journal of Pharmacology, Vol. 57, No. 2-3, 1979, pp. 201-210.
[6] M. J. Detke, M. Rickels and I. Lucki, “Active Behaviors in the Rat Forced Swimming Test Differentially Produced by Serotonergic and Noradrenergic Antidepressants,” Psy- chopharmacology, Vol. 121, No. 1, 1995, pp. 66-72.
[7] S. E. Hemby, I. Lucki, G. Gatto, A. Singh, C. Thornley, J. Matasi, N. Kong, J. E. Smith, H. M. L. Davies and S. I. Dworkin, “Potential Antidepressant Effects of Novel Tro- pane Compounds, Selective for Serotonin or Dopamine Transporters,” Journal of Pharmacology and Experimen- tal Therapeutics, Vol. 282, No. 2, 1997, pp. 727-733.
[8] L. G. Kirby and I. Lucki, “Interaction between the Forced Swimming Test and Fluoxetine Treatment on Extracellu- lar 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid in the Rat,” Journal of Pharmacology and Experimental Therapeutics, Vol. 282, No. 2, 1997, pp. 967-976.
[9] M. E. Page, M. J. Detke, G. Kirby and I. Lucki, “Sero- tonergic Mediation of the Effects of Fluoxetine, but not Desipramine, in the Rat Forced Swimming Test,” Psy- chopharmacology, Vol. 147, No. 2, 1999, pp. 162-167.
[10] J. P. Reneric and I. Lucki, “Antidepressant Behavioral Effects by Dual Inhibition of Monoamine Reuptake in the Rat Forced Swimming Test,” Psychopharmacology, Vol. 136, No. 2, 1998, pp. 190-197.
[11] C. L?pez-Rubalcava and I. Lucki, “Strain Differences in the Behavioral Effects of Antidepressant Drugs in the Rat Forced Swimming Test,” Neuropsychopharmacology, Vol. 22, No. 2, 2000, pp. 191-199.
[12] T. Skrebuhhova, L. Allikmets and V. Matto, “Effect of Anxiogenic Drugs in Rat Forced Swimming Test,” Meth- ods & Findings in Experimental & Clinical Pharmacol- ogy, Vol. 21, No. 3, 1999, pp. 173-178.
[13] J. De Vry, S. Maurel, R. Schreiber, R. de Beun and K. R. Jentzsch, “Comparison of Hypericum Extracts with Imi- pramine and Fluoxetine in Animal Models of Depression and Alcoholism,” European Neuropsychopharmacology, Vol. 9, No. 6, 1999, pp. 461-468.
[14] G. Griebel, C. Cohen, G. Perrault and D. J. Sanger, “Be- havioral Effects of Acute and Chronic Fluoxetine in Wis- tar-Kyoto Rats,” Physiology & Behavior, Vol. 67, No. 3, 1999, pp. 315-320.
[15] J. F. Cryan, M. E. Page and I. Lucki, “Differential Be- havioral Effects of the Antidepressants Reboxetine, Fluo- xetine, and Moclobemide in a Modified Forced Swim Test Following Chronic Treatment,” Psychopharmacol- ogy (Berl), Vol. 182, No. 3, 2005, pp. 335-339.
[16] S. Dal-Zotto, O. Marti and A. Armario, “Influence of Single or Repeated Experience of Rats with Forced Swim- ming on Behavioral and Physiological Responses to the Stressor,” Behavioural Brain Research, Vol. 114, No. 1-2, 2000, pp. 175-181.
[17] L. G. Kirby and I. Lucki, “The Effect of Repeated Expo- sure to Forced Swimming on Extracellular Levels of 5-Hydroxytryptamine in the Rat,” Stress, Vol. 2, No. 4, 1998, pp. 251-263.
[18] A. Parra, C. Vinader-Caerols, S. Monle?n and V. M. Sim?n, “Learned Immobility is also Involved in Forced Swim- ming Test in Mice,” Psicothema, Vol. 11, No. 2, 1999, pp. 239-246.
[19] Y. Lamberty and A. J. Gower, “Cholinergic Modulation of Spatial Learning in Mice in a Morris-Type Water Maze,” Archives Internationales de Pharmacodynamie et de Therapie, Vol. 309, 1991, pp. 5-19.
[20] G. Richter-Levin and M. Segal, “The Effect of Serotonin Depletion and Raphe Grafts on Hippocampal Electro- physiology and Behavior,” Journal of Neuroscience, Vol. 11, No. 6, 1991, pp. 1585-1596.
[21] J. M. De Pablo, A. Parra, S. Segovia and A. Guillamon, “Learned Immobility Explains the Behavior of Rats in the Forced Swimming Test,” Physiology & Behavior, Vol. 46, No. 2, 1989, pp. 229-237.
[22] A. J. Martos, C. Vinader-Caerols, S. Monle?n, M. C. Are- nas and A. Parra, “Effect of Physostigmine and Nicotine on Learned Immobility in the Forced Swimming Test,” Psicothema, Vol. 11, No. 3, 1999, 631-639.
[23] E. H. Cook, K. E. Fletcher, M. Wainwright, N. Marks, S. Y. Yan and B. L. Leventhal, “Primary Structure of the Human Platelet Serotonin 5-HT2A Receptor: Identity with Frontal Cortex Serotonin 5-HT2A Receptor,” Journal of Neurochemistry, Vol. 63, No. 2, 1994, pp. 465-469.
[24] C. R. Pfeffer, P. A. McBride, G. M. Anderson, T. Ka- kuma, L. Fensterheim and V. Khait, “Peripheral Sero- tonin Measures in Prepubertal Psychiatric Inpatients and Normal Children: Association with Suicidal Behavior and its Risk Factors,” Biological Psychiatry, Vol. 44, No. 7, 1988, pp. 568-577.
[25] S. D. Mendelson, “The Current Status of the Platelet 5-HT2A Receptor in Depression,” Journal of Affective Disorders, Vol. 57, No. 1, 2000, pp. 13-24.
[26] J. M. Sneddon, “Blood Platelets as a Model for Mono- amine Containing Neurones,” Progress in Neurobiology, Vol. 1, No. 2, 1973, pp. 151-198.
[27] S. M. Stahl, “The Human Blood Platelet: A Diagnostic and Research Tool for the Study of Biogenic Amines in Psychiatric and Neurologic Disorders,” Archives of Gen- eral Psychiatry, Vol. 34, No. 5, 1977, pp. 509-516.
[28] M. Bianchi, C. Moser, C. Lazzarini, E. Vecchiato and F. Crespi, “Forced Swimming Test and Fluoxetine Treat- ment: In Vivo Evidence that Peripheral 5-HT in Rat Platelet-Rich Plasma Mirrors Cerebral Extracellular 5-HT Levels, whilst 5-HT in Isolated Platelets Mirrors Neu- ronal 5-HT Changes,” Experimental Brain Research, Vol. 143, No. 2, 2002, pp. 191-197.
[29] F. Congestri, F. Formenti, V. Sonntag and F. Crespi, “The Selective D3 Receptor Antagonist SB-277011-A Potenti- ates the Effect of Cocaine on Extracellular Dopamine in the Nucleus Accumbens: A Dual Core-Shell Voltammetry Study in Anesthetized Rats,” Sensors, Vol. 8, No. 11, 2008, pp. 6936-6951.
[30] F. Crespi, “In Vivo Voltammetry with Micro-Biosensors for Analysis of Neurotransmitter Release and Metabo- lism,” Journal of Neuroscience Methods, Vol. 34, No. 1-3, 1990, pp. 53-65.
[31] F. Crespi, K. F. Martin and C. A. Marsden, “Measurement of Extracellular Basal Levels of Serotonin in Vivo Using Nafion-Coated Carbon Fibre Electrodes Combined with Differential Pulse Voltammetry,” Neuroscience, Vol. 27, No. 3, 1988, pp. 885-896.
[32] J.-M. Zen, I.-L. Chen and Y. Shih, “Voltammetric Deter- mination of Serotonin in Human Blood Using a Chemi- cally Modified Electrode,” Analytica Chimica Acta, Vol. 369, No. 1-2, 1998, pp. 103-108.
[33] F. Crespi, “In Vivo Voltammetry and Concomitant Elec- trophysiology at a Single Biosensor to Analyse Ischaemia, Depression and Drug Dependence,” Journal of Neuro- science Methods, Vol. 119, No. 2, 2002, pp. 173-184.
[34] F. Crespi and M. Jouvet, “Differential Pulse Voltammetry Parallel Peak 3 Changes with Vigilance States in Raphe Dorsalis and Raphe Magnus of Chronic Freely Moving Rats and Evidence for 5HT Contribution to this Peak after Monoamine Oxidase Inhibitors,” Brain Research, Vol. 272, No. 2, 1983, pp. 263-268.
[35] A. Louilot, A. Serrano and M. D’Angio, “A Novel Car- bon Fiber Implantation Assembly for Cerebral Voltam- metric Measurements in Freely Moving Rats,” Physiology & Behavior, Vol. 41, No. 3, 1987, pp. 227-231.
[36] S. L. Handley and J. W. McBlane, “Opposite Effects of Fluoxetine in Two Animal Models of Anxiety,” British Journal of Pharmacology, Vol. 107S, 1997, p. 446.
[37] M. L. Rao, B. Hawellek, A. Papassotiropoulos, A. Deister and C. Frahnert, “Upregulation of the Platelet Serotonin2A Receptor and Low Blood Serotonin in Suicidal Psychiat- ric Patients,” Neuropsychobiology, Vol. 38, No. 2, 1998, pp. 84-89.
[38] F. Crespi, “Apamin Increases 5-HT Cell Firing in Raphe Dorsalis and Extracellular 5-HT Levels in Amygdala: A Concomitant in Vivo Study in Anesthetized Rats,” Brain Research, Vol. 1281, 2009, pp. 35-46.
[39] K. F. Martin, C. A. Marsden and F. Crespi. “In Vivo Electrochemistry with Carbon Fibre Electrodes: Princi- ples and Application to Neuropharmacology,” Trends in Analytical Chemistry, Vol. 7, No. 9, 1988, pp. 334-339.
[40] J. A. Stamford, F. Crespi and C. A. Marsden, “In Vivo Voltammetric Methods for Monitoring Monoamine Re- lease and Metabolism,” Monitoring Neuronal Activity, a Practical Approach, Oxford University Press, Oxford, 1992, pp. 113-145.
[41] T Self and F. Crespi, “Electron Microscopic and Volt- ammetric Analysis of Carbon Fibre Electrode Pretreat- ments,” Journal of Materials Science: Materials in Medi- cine, Vol. 3, No. 6, 1992, pp. 418-425.
[42] F. Crespi and Z. L. Rossetti, “Pulse of Nitric Oxide Re- lease in Response to Activation of N-Methyl-D-Aspartate Receptors in the Rat Striatum: Rapid Desensitisation, In- hibition by Receptor Antagonists and Potentiation by Glycine,” Journal of Pharmacology and Experimental Therapeutics, Vol. 309, No. 2, 2004, pp. 462-468.
[43] F. Crespi, T. Sharp, N. Maidment and C. A. Marsden, “Differential Pulse Voltammetry in Vivo–Evidence that Uric Acid Contributes to the Indole Oxidation Peak,” Neuroscience Letters, Vol. 43, No. 2-3, 1983, pp. 203-207.
[44] F. Crespi, T. Sharp, N. Maidment and C. A. Marsden, “Dif- ferential Pulse Voltammetry: Simultaneous in Vivo Meas- urement of Ascorbic Acid, Catechols and 5-Hydroxyindoles in the Rat Striatum Using a Single Carbon Fibre Elec- trode,” Brain Research, Vol. 322, No. 1, 1984, pp. 135- 138.
[45] F. Crespi, P. Keane and M. Morre, “Does Concomitant Analysis of Extracellular DOPAC and 5HIAA with a Sin- gle Carbon Fibre Electrode Enable the Detection of Stri- atal Dopamine-Serotonin Interaction?” Journal of Neu- rochemistry, 1985, Vol. 44, pp. 109-112.
[46] F. Borsini, “Role of the Serotonergic System in the Forced Swimming Test,” Neuroscience & Biobehavioral Reviews, Vol. 19, No. 3, 1995, pp. 377-395.
[47] W. F. Boyer and J. P. Feighner, “Side Effects of the Se- lective Serotonin Re-Uptake Inhibitors,” In: J. P. Feigh- ner and W. F. Boyer, Ed., Selective Serotonin Re-Uptake Inhibitors. Perspectives in Psychiatry 1, Wiley Press, New York, 1991, pp. 133-152.
[48] P. Chopin and M. Briley, “Animal Models of Anxiety: The Effect of Compounds that Modify 5-HT Neurotrans- mission,” Trends in Pharmacological Sciences, Vol. 8, No. 10, 1987, pp. 383-388.
[49] F. Borsini, A. Lecci, A. Sessarego, R. Frassine and A. Meli, “Discovery of Antidepressant Activity by Forced Swimming Test may Depend on Pre-Exposure of Rats to a Stressful Situation,” Psychopharmacology, Vol. 97, No. 2, 1989, pp. 183-188.
[50] C. Barja-Fidalgo, J. A. Guimaraes and C. R. Carlini, “The Secretory Effect of Canatoxin on Rat Brain Synaptosomes Involves A Lipoxygenase-Mediated Pathway,” Brazilian Journal of Medical and Biological Research, Vol. 21, No. 3, 1988, pp. 549-552.
[51] R. M. Lyons and J. O. Shaw, “Interaction of Ca 2+ and Protein Phosphorylation in the Rabbit Platelet Release Reaction,” Journal of Clinical Investigation, Vol. 65, No. 2, 1980, pp. 242-255.
[52] H. C. Buhot, S. Martin and L. Segu, “Role of Serotonin in Memory Impairment,” Annals of Medicine, Vol. 32, No. 3, 2000, pp. 210-221.
[53] W. J. McEntee and T. H. Crook, “Serotonin, Memory, and the Aging Brain,” Psychopharmacology, Vol. 103, No. 2, 1991, pp. 143-149.
[54] I. Gonzalez-Burgos, M. I. Perez-Vega, A. R. Del Angel- Meza and A. Feria-Velasco, “Effect of Tryptophan Re- striction on Short-Term Memory,” Physiology & Behav- ior, Vol. 63, No. 2, 1998, pp. 165-169.
[55] G. T. Shishkina, T. S. Kalinina and N. N. Dygalo, “Sero- tonergic Changes Produced by Repeated Exposure to Forced Swimming: Correlation with Behavior,” Annals of the New York Academy of Sciences, Vol. 1148, 2008, pp. 148-153.
[56] M. H. Maes and Y. Meltzer, “The Serotonin Hypothesis of Major Depression,” In: F. E. Bloom and D. J. Kupfer, Ed., Psychopharmacology: The Fourth Generation of Pro- gress, Raven Press, New York, 1995, pp. 933-944.
[57] F. Chaouloff, “Physiopharmacological Interactions between Stress Hormones and Central Serotonergic Systems,” Brain Research Reviews, Vol. 18, No. 1, 1993, pp. 1-32.
[58] L. E. Rueter, C. A. Fornal and B. L. Jacobs, “A Critical Review of 5-HT Brain Microdialysis and Behavior,” Re- views in the Neurosciences, Vol. 8, No. 2, 1997, pp. 117-137.
[59] R. K. McNamara and R. W. Skelton, “The Neurophar- macological and Neurochemical Basis of Place Learning in the Morris Water Maze,” Brain Research Reviews, Vol. 18, No. 1, 1993, pp. 33-49.
[60] S. Tejani-Butt, J. Kluczynski and W. P. Paré, “Strain- Dependent Modification of Behavior Following Antide-pressant Treatment,” Progress in Neuro-Psychopharma- cology & Biological Psychiatry, Vol. 27, No. 1, 2003, pp. 7-14.
[61] O. Malkesman, Y. Braw, R. Maayan, A. Weizman, D. H. Overstreet, M. Shabat-Simon, Y. Kesner, et al., “Two Different Putative Genetic Animal Models of Childhood Depression,” Biological Psychiatry, Vol. 59, No. 1, 2006, pp. 17-23.
[62] B. L. Roth, S. M. Hanizavareh and A. E. Blum, “Sero- tonin Receptors Represent Highly Favorable Molecular Targets for Cognitive Enhancement in Schizophrenia and Other Disorders,” Psychopharmacology, Vol. 174, No. 1, 2004, pp. 17-24.
[63] E. S. Mitchell and J. F. Neumaier, “5-HT6 Receptors: A Novel Target for Cognitive Enhancement,” Pharmacol- ogy & Therapeutics, Vol. 108, No. 3, 2005, pp. 320-333.
[64] R. Schreiber, A. J. Sleight and M. L. Woolley, “5-HT6 Receptors as Targets for the Treatment of Cognitive Deficits in Schizophrenia,” In: B. R. Roth, Ed., Serotonin Receptors: From Molecular Pharmacology to Human Ther- apeutics, Humana Press, Totowa, 2006, pp. 495-515.
[65] E. S. Mitchell, B. J. Hoplight, S. P. Lear and J. F. Neu- maier, “BGC20-761, a Novel Tryptamine Analog, En- hances Memory Consolidation and Reverses Scopola- mine-Induced Memory Deficit in Social and Visuospatial Memory Tasks through a 5-HT6 Receptor-Mediated Me- chanism,” Neuropharmacology, Vol. 50, No. 4, 2006, pp. 412-420.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.