Citalopram elicits a discriminative stimulus in rats at a dose selectively increasing extracellular levels of serotonin vs. dopamine and noradrenaline

Citalopram (2.5 mg/kg, i.p.) increased (+145-+180%) extracellular levels of serotonin (5-hydroxytryptamine, 5-HT) in the frontal cortex, nucleus accumbens and striatum of freely-moving rats, whereas dopamine and noradrenaline were unaffected. At this dose, employing a two-lever, food-reinforced, drug discrimination procedure, citalopram generated reliable recognition and fully (> 80%) generalized to itself with an Effective Dose50 (ED50) of 0.1 mg/kg, s.c. Two further selective 5-HT reuptake inhibitors, sertraline and paroxetine, fully generalized with ED50s of 0.01 and 0.04 mg/kg, s.c., respectively. In contrast, the anxiolytic, diazepam (0.63), and the antipsychotic, clozapine (2.5), did not (< or = 20%) generalize. In conclusion, the selective 5-HT reuptake inhibitor, citalopram, elicits a pharmacologically-specific discriminative stimulus in rats at a dose selectively elevating extracellular concentrations of 5-HT.