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Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test.
Neuropsychopharmacology. 2001 Apr; 24(4):379-90.N

Abstract

The rat forced swimming test (FST) predicts the efficacy of antidepressants, which decrease immobility duration in the test, and can distinguish selective serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors, which, respectively, increase swimming and climbing behaviors. However, dual 5-HT and NA reuptake-inhibition produces climbing behavior solely, thereby suggesting with other data that the NA-system mediates inhibiting interactions on 5-HT-induced swimming in the FST. Since alpha(2)-adrenoreceptors and 5-HT(1A)-receptors have important regulatory functions and are involved in 5-HT/NA interactions, we examined whether the alpha(2)-receptor-antagonist idazoxan and the 5-HT(1A)-receptor-agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) would modify the behavioral pattern induced in the FST by either selective or non-selective antidepressant treatments. The rats were treated subacutely (3 injections IP over 48 h) with: (a) idazoxan (0.5-10 mg/kg) alone, and in combination with desipramine (10 mg/kg), or desipramine + fluoxetine (10/10 mg/kg), or the dual serotonin/noradrenaline reuptake-inhibitor milnacipran (20 mg/kg). (b) 8-OH-DPAT (0.25-1 mg/kg) alone, and in combination with either desipramine (10 mg/kg) or fluoxetine (10 mg/kg). The results indicated: (a) Idazoxan (0.5, 5, 10 mg/kg) produced no anti-immobility effects per se in the FST, antagonized the effects of the NA-reuptake-inhibitor desipramine, and allowed desipramine + fluoxetine, as well as milnacipran, to increase swimming behavior. (b) 8-OH-DPAT produced non-significant effects per se, potentiated desipramine-induced antidepressant-like effects on immobility and climbing, and both antagonized swimming and produced climbing behavior in combination with fluoxetine. Our data support clinical trials suggesting that alpha(2)-receptor-antagonists and 5-HT(1A)-receptor-agonists may be of interest in augmentation strategies for antidepressant treatments. The scoring of active behaviors in the FST appears to be an interesting tool for studying 5-HT/NA interactions induced by antidepressants, as well as for the testing of augmentation strategies.

Authors+Show Affiliations

Laboratoire de Neuropsychobiologie des Désadaptations, CNRS-UMR 5541, Université Bordeaux2, [DNY], Bordeaux, France. Jean-Philippe.Reneric@labopsy.u-bordeaux2.frNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11182533

Citation

Rénéric, J P., et al. "Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced By Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 24, no. 4, 2001, pp. 379-90.
Rénéric JP, Bouvard M, Stinus L. Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test. Neuropsychopharmacology. 2001;24(4):379-90.
Rénéric, J. P., Bouvard, M., & Stinus, L. (2001). Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 24(4), 379-90.
Rénéric JP, Bouvard M, Stinus L. Idazoxan and 8-OH-DPAT Modify the Behavioral Effects Induced By Either NA, or 5-HT, or Dual NA/5-HT Reuptake Inhibition in the Rat Forced Swimming Test. Neuropsychopharmacology. 2001;24(4):379-90. PubMed PMID: 11182533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Idazoxan and 8-OH-DPAT modify the behavioral effects induced by either NA, or 5-HT, or dual NA/5-HT reuptake inhibition in the rat forced swimming test. AU - Rénéric,J P, AU - Bouvard,M, AU - Stinus,L, PY - 2001/2/22/pubmed PY - 2001/5/26/medline PY - 2001/2/22/entrez SP - 379 EP - 90 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 24 IS - 4 N2 - The rat forced swimming test (FST) predicts the efficacy of antidepressants, which decrease immobility duration in the test, and can distinguish selective serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors, which, respectively, increase swimming and climbing behaviors. However, dual 5-HT and NA reuptake-inhibition produces climbing behavior solely, thereby suggesting with other data that the NA-system mediates inhibiting interactions on 5-HT-induced swimming in the FST. Since alpha(2)-adrenoreceptors and 5-HT(1A)-receptors have important regulatory functions and are involved in 5-HT/NA interactions, we examined whether the alpha(2)-receptor-antagonist idazoxan and the 5-HT(1A)-receptor-agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) would modify the behavioral pattern induced in the FST by either selective or non-selective antidepressant treatments. The rats were treated subacutely (3 injections IP over 48 h) with: (a) idazoxan (0.5-10 mg/kg) alone, and in combination with desipramine (10 mg/kg), or desipramine + fluoxetine (10/10 mg/kg), or the dual serotonin/noradrenaline reuptake-inhibitor milnacipran (20 mg/kg). (b) 8-OH-DPAT (0.25-1 mg/kg) alone, and in combination with either desipramine (10 mg/kg) or fluoxetine (10 mg/kg). The results indicated: (a) Idazoxan (0.5, 5, 10 mg/kg) produced no anti-immobility effects per se in the FST, antagonized the effects of the NA-reuptake-inhibitor desipramine, and allowed desipramine + fluoxetine, as well as milnacipran, to increase swimming behavior. (b) 8-OH-DPAT produced non-significant effects per se, potentiated desipramine-induced antidepressant-like effects on immobility and climbing, and both antagonized swimming and produced climbing behavior in combination with fluoxetine. Our data support clinical trials suggesting that alpha(2)-receptor-antagonists and 5-HT(1A)-receptor-agonists may be of interest in augmentation strategies for antidepressant treatments. The scoring of active behaviors in the FST appears to be an interesting tool for studying 5-HT/NA interactions induced by antidepressants, as well as for the testing of augmentation strategies. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/11182533/Idazoxan_and_8_OH_DPAT_modify_the_behavioral_effects_induced_by_either_NA_or_5_HT_or_dual_NA/5_HT_reuptake_inhibition_in_the_rat_forced_swimming_test_ L2 - http://dx.doi.org/10.1016/S0893-133X(00)00214-1 DB - PRIME DP - Unbound Medicine ER -