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Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat.

Abstract

Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2) and monoamine releaser, so it can be used as a pharmacological model of depression. In the present paper, we investigated the behavioral and neurochemical effects of withdrawal from acute and repeated administration of a low dose of reserpine (0.2 mg/kg) in Wistar Han rats. We demonstrated the behavioral and receptor oversensitivity (postsynaptic dopamine D1) during withdrawal from chronic reserpine. It was accompanied by a significant increase in motility in the locomotor activity test and climbing behavior in the forced swim test (FST). Neurochemical studies revealed that repeated but not acute administration the a low dose of reserpine triggered opposing adaptive changes in the noradrenergic and serotonin system function analyzed during reserpine withdrawal, i.e. 48 h after the last injection. The tissue concentration of noradrenaline was significantly decreased in the hypothalamus and nucleus accumbens only after repeated drug administration (by about 20% and 35% vs. control; p<0.05, respectively). On the other hand, the concentration of its extraneuronal metabolite, normetanephrine (NM) increased significantly in the VTA during withdrawal both from acute and chronic reserpine. The serotonin concentration was significantly reduced in the VTA after chronic reserpine (by about 40% vs. the control group, p<0.05) as well as its main metabolite, 5-HIAA (by about 30% vs. control; p<0.05) in the VTA and hypothalamus. Dopamine and its metabolites were not changed after acute or chronic reserpine administration. In vivo microdialysis studies clearly evidenced the lack of the effect of a single dose of reserpine, and its distinct effects after chronic treatment on the release of noradrenaline and serotonin in the rat striatum. In fact, the withdrawal from repeated administration of reserpine significantly increased an extraneuronal concentration of noradrenaline in the rat striatum but at the same time produced a distinct fall in the extraneuronal serotonin in this brain structure. On the basis of the presented behavioral and neurochemical experiments, we suggest that chronic administration of reserpine even in such low dose which not yet acted on the release of monoamines but produced an inhibition of VMAT2 caused a long-lasting disadvantageous effect of plasticity in the brain resembling depressive disorders.

Authors+Show Affiliations

Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland. Electronic address: antkiew@if-pan.krakow.pl.Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25445479

Citation

Antkiewicz-Michaluk, Lucyna, et al. "Withdrawal From Repeated Administration of a Low Dose of Reserpine Induced Opposing Adaptive Changes in the Noradrenaline and Serotonin System Function: a Behavioral and Neurochemical Ex Vivo and in Vivo Studies in the Rat." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 57, 2015, pp. 146-54.
Antkiewicz-Michaluk L, Wąsik A, Możdżeń E, et al. Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2015;57:146-54.
Antkiewicz-Michaluk, L., Wąsik, A., Możdżeń, E., Romańska, I., & Michaluk, J. (2015). Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat. Progress in Neuro-psychopharmacology & Biological Psychiatry, 57, pp. 146-54. doi:10.1016/j.pnpbp.2014.10.009.
Antkiewicz-Michaluk L, et al. Withdrawal From Repeated Administration of a Low Dose of Reserpine Induced Opposing Adaptive Changes in the Noradrenaline and Serotonin System Function: a Behavioral and Neurochemical Ex Vivo and in Vivo Studies in the Rat. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:146-54. PubMed PMID: 25445479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat. AU - Antkiewicz-Michaluk,Lucyna, AU - Wąsik,Agnieszka, AU - Możdżeń,Edyta, AU - Romańska,Irena, AU - Michaluk,Jerzy, Y1 - 2014/11/08/ PY - 2014/07/14/received PY - 2014/10/15/revised PY - 2014/10/21/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/8/14/medline KW - Brain structures KW - Dopamine D1 and D2 receptors KW - Forced swim test KW - In vivo release of monoamines KW - Metabolism of monoamines KW - Reserpine model of depression SP - 146 EP - 54 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 57 N2 - Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2) and monoamine releaser, so it can be used as a pharmacological model of depression. In the present paper, we investigated the behavioral and neurochemical effects of withdrawal from acute and repeated administration of a low dose of reserpine (0.2 mg/kg) in Wistar Han rats. We demonstrated the behavioral and receptor oversensitivity (postsynaptic dopamine D1) during withdrawal from chronic reserpine. It was accompanied by a significant increase in motility in the locomotor activity test and climbing behavior in the forced swim test (FST). Neurochemical studies revealed that repeated but not acute administration the a low dose of reserpine triggered opposing adaptive changes in the noradrenergic and serotonin system function analyzed during reserpine withdrawal, i.e. 48 h after the last injection. The tissue concentration of noradrenaline was significantly decreased in the hypothalamus and nucleus accumbens only after repeated drug administration (by about 20% and 35% vs. control; p<0.05, respectively). On the other hand, the concentration of its extraneuronal metabolite, normetanephrine (NM) increased significantly in the VTA during withdrawal both from acute and chronic reserpine. The serotonin concentration was significantly reduced in the VTA after chronic reserpine (by about 40% vs. the control group, p<0.05) as well as its main metabolite, 5-HIAA (by about 30% vs. control; p<0.05) in the VTA and hypothalamus. Dopamine and its metabolites were not changed after acute or chronic reserpine administration. In vivo microdialysis studies clearly evidenced the lack of the effect of a single dose of reserpine, and its distinct effects after chronic treatment on the release of noradrenaline and serotonin in the rat striatum. In fact, the withdrawal from repeated administration of reserpine significantly increased an extraneuronal concentration of noradrenaline in the rat striatum but at the same time produced a distinct fall in the extraneuronal serotonin in this brain structure. On the basis of the presented behavioral and neurochemical experiments, we suggest that chronic administration of reserpine even in such low dose which not yet acted on the release of monoamines but produced an inhibition of VMAT2 caused a long-lasting disadvantageous effect of plasticity in the brain resembling depressive disorders. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/25445479/Withdrawal_from_repeated_administration_of_a_low_dose_of_reserpine_induced_opposing_adaptive_changes_in_the_noradrenaline_and_serotonin_system_function:_a_behavioral_and_neurochemical_ex_vivo_and_in_vivo_studies_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(14)00200-0 DB - PRIME DP - Unbound Medicine ER -