Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using a rodent five-choice reaction time task.

RATIONALE: Converging evidence suggests that dopaminergic and serotonergic mechanisms affect distinct aspects of cognitive performance. Experiments using the rodent five-choice reaction time task have established a critical role for dopaminergic mechanisms in the rat medial prefrontal cortex (mPFC), but have yielded only incomplete evidence regarding the specific functions of serotonin receptors.
OBJECTIVES: To contrast the effects of systemic or intra-mPFC administration of dopamine or serotonin agents on performance of the five-choice reaction time task.
METHODS: Two groups of rats trained on the five-choice reaction time task received systemic administration of either the dopamine D(1) receptor partial agonist SKF 38393 (0, 1, 3 or 10 mg/kg IP) or the serotonin 5-HT(2A/C) receptor antagonist ketanserin (0, 0.3, 0.6 or 1 mg/kg SC) prior to testing; a further group was implanted with chronic guide cannulae and received ketanserin (0, 0.025, 0.1 or 0.4 micro g/side) infused into the mPFC prior to testing.
RESULTS: SKF 38393 affected aspects of accuracy and vigour of responding, while regardless of the route of administration ketanserin reduced premature responding without any effect on choice accuracy.
CONCLUSIONS: Together with our previous findings of increased choice accuracy following intra-mPFC SKF 38393 (Granon et al. 2000), the present results support the notion that the functions of dopamine and serotonin receptors in the mPFC relate to two distinct domains of executive control. Dopamine D(1) receptors are critical to optimise response selection in skilled non-automatic tasks, while serotonin 5-HT(2A) receptors regulate the execution of primed responses.