Neuropharmacology and analgesiaEffects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum

Prefrontal catecholamine neurotransmission plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). We have recently shown that serotonin/noradrenaline reuptake inhibitors and the noradrenaline reuptake inhibitor desipramine attenuated horizontal hyperactivity in spontaneously hypertensive rats, an animal model of ADHD, and that these drugs are potential pharmacotherapeutics for ADHD. In this study, we used in vivo microdialysis to study the effects of acute and chronic (once daily for 3 weeks) administration of the serotonin/noradrenaline reuptake inhibitor venlafaxine and the noradrenaline reuptake inhibitor desipramine on noradrenaline, dopamine, and serotonin levels, and the expression of the neuronal activity marker c-Fos in the mouse prefrontal cortex and striatum. Both acute and chronic venlafaxine administration increased prefrontal noradrenaline, dopamine, and serotonin levels and striatal noradrenaline and serotonin levels. Both acute and chronic desipramine administration increased prefrontal noradrenaline and dopamine levels and striatal noradrenaline levels, with chronic administration yielding stronger increase. Chronic desipramine did not affect striatal dopamine and serotonin levels. Both acute and chronic venlafaxine administration increased the expression of c-Fos in the prefrontal cortex, whereas chronic, but not acute, desipramine administration increased the expression of c-Fos in the prefrontal cortex. Both acute and chronic venlafaxine administration increased the striatal c-Fos expression to some degree, whereas desipramine administration did not. These results suggest that acute and chronic venlafaxine and chronic desipramine administration maximally activate the prefrontal adrenergic and dopaminergic systems without affecting striatal dopaminergic systems in mice.