title: Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats.
abstract: BACKGROUND
  The neuropeptide Y (NPY) system acts in synergy with the classic neurotransmitters to regulate a large variety of functions including autonomic, affective, and cognitive processes. Research on the effects of NPY in the central nervous system has focused on food intake control and affective processes, but growing evidence of NPY involvement in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric conditions motivated the present study.
  
  
  OBJECTIVE
  We tested the effects of the novel and highly selective NPY Y5 receptor antagonist Lu AE00654 on impulsivity and the underlying cortico-striatal circuitry in rats to further explore the possible involvement of the NPY system in pathologies characterized by inattention and impulsive behavior.
  
  
  RESULTS
  A low dose of Lu AE00654 (0.03 mg/kg) selectively facilitated response inhibition as measured by the stop-signal task, whereas no effects were found at higher doses (0.3 and 3 mg/kg). Systemic administration of Lu AE00654 also enhanced the inhibitory influence of the dorsal frontal cortex on neurons in the caudate-putamen, this fronto-striatal circuitry being implicated in the executive control of behavior. Finally, by locally injecting a Y5 agonist, we observed reciprocal activation between dorsal frontal cortex and caudate-putamen neurons. Importantly, the effects of the Y5 agonist were attenuated by pretreatment with Lu AE00654, confirming the presence of Y5 binding sites modulating functional interactions within frontal-subcortical circuits.
  
  
  CONCLUSIONS
  These results suggest that the NPY system modulates inhibitory neurotransmission in brain areas important for impulse control, and may be relevant for the treatment of pathologies such as ADHD and drug abuse.
authors.affiliation: Behavioral and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK, baria@mit.edu.
authors.forename: A
authors.initials: A
authors.lastname: Bari
authors.forename: A
authors.initials: A
authors.lastname: Dec
authors.forename: A W
authors.initials: AW
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Song
authors.forename: E
authors.initials: E
authors.lastname: Dale
authors.forename: J
authors.initials: J
authors.lastname: Peterson
authors.forename: S
authors.initials: S
authors.lastname: Zorn
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: B
authors.initials: B
authors.lastname: Campbell
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.forename: A R
authors.initials: AR
authors.lastname: West
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor