Differential effects of adjunctive methylphenidate and citalopram on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain

Several clinical studies have suggested that the combined treatment with methylphenidate and citalopram may accelerate the onset of antidepressant action and induce an improvement even in treatment-refractory patients. In the present study, in vivo microdialysis was used to monitor the extracellular levels of serotonin, noradrenaline and dopamine in the prefrontal cortex, hippocampus, nucleus accumbens and striatum of the rat. Administration of methylphenidate (2.5 mg/kg s.c.) with citalopram (5 mg/kg i.p.) compared to methylphenidate alone caused a marked enhancement of dopamine levels in the prefrontal cortex, n. accumbens and hippocampus, but not in the striatum. Citalopram-induced increase in serotonin levels was strongly enhanced by adjunctive methylphenidate in the hippocampus, but attenuated in the cortex. These findings suggest that the proposed augmentation effects of adjuvant methylphenidate to citalopram are most likely associated with enhanced dopamine transmission in the corticolimbic areas, whereas serotonin and noradrenaline levels show differential and region specific responses. (C) 2007 Elsevier B.V. and ECNP. All rights reserved.