Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor.

We previously reported that chronic, but not subchronic, treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine altered behavior in the forced swimming test (FST) in BALB/cJ mice. We now use this model to investigate mechanisms underlying the delayed onset of the behavioral response to antidepressants, specifically (1) adult hippocampal neurogenesis and (2) expression of the 5-HT1A receptor. Here, we show data validating this model of chronic antidepressant action.

Effects of chronic fluoxetine in animal models of anxiety and depression.

The onset of the therapeutic response to antidepressant treatment exhibits a characteristic delay. Animal models sensitive to chronic, but not acute, antidepressant treatment are greatly needed for studying antidepressant mechanisms. We initially assessed four inbred mouse strains for their behavioral response to chronic treatment with the selective-serotonin reuptake inhibitor fluoxetine (0, 5, 10 mg/kg/day in drinking water), which is used for the treatment of mood and anxiety disorders.

p38 MAP kinase mediates both short-term and long-term synaptic depression in aplysia.

At Aplysia sensory-to-motor neuron synapses, the inhibitory neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa) produces depression, and serotonin (5-HT) produces facilitation. Short-term depression has been found to result from the activation of a phospholipase A2. The released arachidonate is metabolized by 12-lipoxygenase to active second messengers.