Intra-accumbens infusions of antisense oligodeoxynucleotides to one isoform of glutamic acid decarboxylase mRNA, GAD(65), but not to GAD(67), mRNA, impairs sustained attention performance in the rat

The effects of bilateral infusions of antisense oligodeoxynucleotides (ODNs ) for the two isoforms of glutamic acid decarboxylase (GAD(65); GAD(67)) in to the nucleus accumbens on the performance of intact rats in a task design ed to assess sustained attention were tested. The task required the animals to discriminate between signal and non-signal events. Signals and non-sign als were presented randomly and unpredictably. The task generated all four response types of a sustained attention task, i.e., hits, misses, correct r ejections, false alarms. Infusions of the scrambled sequence ODNs did not a ffect performance. Likewise, infusions of the GAD(67) ODNs failed to produc e any effect. However, infusions of the GAD(65) ODNs into the nucleus accum bens resulted in a robust and reliable decrease in the relative number of h its. Similarly, the combined infusion of GAD(65+67) ODNs impaired the hit r ate but did not affect the animals' ability to reject non-signals. Followin g each treatment series, performance rapidly returned to baseline, further indicating the specificity and reversibility of the effects of the infusion s of the ODNs. While these data suggest that translation arrest of specific ally the GAD(65) isoform of the enzyme in the nucleus accumbens impairs att entional performance, the neuronal mechanisms mediating these effects remai n unsettled. (C) 1999 Elsevier Science B.V. All rights reserved.