Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype.
Neuropeptide (NPY) Y2 receptors play an important role in some anxiety-related and stress-related behaviours in mice. Changes in the level of anxiety can affect some cognitive functions such as memory, attention and inhibitory response control. We investigated the effects of NPY Y2 receptor deletion (Y2(-/-)) in mice on visual attention and response control using the five-choice serial reaction time (5-CSRT) task in which accuracy of detection of a brief visual stimulus across five spatial locations may serve as a valid behavioural index of attentional functioning. Anticipatory and perseverative responses provide a measure of inhibitory response control. During training, the Y2(-/-) mice had lower accuracy (% correct), and made more anticipatory responses. At stimulus durations of 2 and 4s the Y2(-/-) were as accurate as the Y2(+/+) mice but still more impulsive than Y(+/+). At stimulus durations of 0.25 and 0.5s both groups performed worse but the Y2(-/-) mice made significantly fewer correct responses than the Y2(+/+) controls. The anxiolytic drug diazepam at 2mg/kg IP greatly increased the anticipatory responding of Y2(-/-) mice compared to Y2(+/+). The anxiogenic inverse benzodiazepine agonist, FG 7142, at 10mg/kg IP reduced the anticipatory responding of Y2(-/-) but not Y2(+/+) mice. These data suggest that NPY Y2 receptors make an important contribution to mechanisms controlling attentional functioning and "impulsivity". They also show that "impulsivity" of NPY Y2(-/-) mice may depend on their level of anxiety. These findings may help in understanding the pathophysiology of stress disorders and depression.
Greco
Barbara
B
Department of Neuroscience, Istituto di Ricerche Farmacologiche "Mario Negri", via Eritrea 62, 20157 Milano, Italy.
Carli
Mirjana
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology*; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002243:Carbolines / Q000627:therapeutic use; D002755:Choice Behavior / Q000502:physiology; D003975:Diazepam / Q000627:therapeutic use; D007175:Impulsive Behavior / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011930:Reaction Time / Q000235:genetics; D017476:Receptors, Neuropeptide Y / Q000172:deficiency*; D012054:Reinforcement, Psychology; D013647:Task Performance and Analysis; D013997:Time Factors
D014151:Anti-Anxiety Agents; D002243:Carbolines; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; C035874:FG 7142; D003975:Diazepam