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
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.