Effects of 5-HT depletion in the frontal cortex or nucleus accumbens on response inhibition measured in the 5-choice serial reaction time test and on a DRL schedule

Previous work has shown that global depletion of brain serotonin (5-HT) using the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) increases impulsive like behaviour measured as premature responding on the 5-choice serial reaction time (5-CSRT) test, and inefficient responding on a DRL20 schedule of food reinforcement. The present experiments examined whether these effects could be attributed to loss of 5-HT inputs to either the frontal cortex (FC) or the nucleus accumbens. Infusing 5,7-DHT into the FC depleted 5-HT by more than 80%. This did not alter premature responding on the 5-CSRT test, although the number of trials on which responses were omitted was reduced by this manipulation. Depletion of 5-HT in the FC did not alter responding on the DRL20 schedule, nor when the schedule value was increased to 40 s. Infusing 5,7-DHT into the nucleus accumbens depleted 5-HT by greater than 80%, and modestly reduced 5-HT in the FC also. Depletion of 5-HT in the nucleus accumbens did not affect premature responding on the 5-CSRT test in rats trained on this test prior to the lesion. Acquisition of responding on this test was also not affected by this lesion. On the DRL20 schedule response rate was increased and the mean inter-response interval was significantly reduced in lesioned animals. Loss of 5-HT inputs to the FC does not appear to alter response inhibition, whereas loss of 5-HT innervation to the nucleus accumbens only affected inhibitory control on the DRL schedule. The behavioural profile of global 5-HT depletion cannot be accounted for by selective loss of 5-HT innervation to either the FC or the nucleus accumbens. (C) 2009 Elsevier B.V. All rights reserved.