Neuropeptide Y Y1 receptor-mediated anxiolysis in the dorsocaudal lateral septum: functional antagonism of corticotropin-releasing hormone-induced anxiety.
Neuropeptide Y and corticotropin-releasing hormone are involved in the regulation of various physiological functions including the expression of anxiety and fear. The anxiogenic effects of corticotropin-releasing hormone can be modulated by neuropeptide Y, yet the brain regions involved in this interaction are only partly understood. By utilizing antibodies raised against neuropeptide Y and the Y1 receptor protein we identified a densely labeled cell group in the dorsal zone of caudal part of the rat lateral septum. Bilateral microinjections of neuropeptide Y into the dorsocaudal lateral septum but not into the intramedial septum dose-dependently decreased anxiety in the social interaction test of rats, whereas the effects of corticotropin-releasing hormone were opposite. The anxiogenic-like effect of corticotropin-releasing hormone was reversed by neuropeptide Y pretreatment. Local microinjection of the neuropeptide Y receptor selective antagonists revealed that neither Y1 receptor nor Y2 receptor selective antagonists had effects on experimental anxiety on their own suggesting that neuropeptide Y-induced anxiolysis is not tonic. The Y1 receptor antagonist blocked the anxiolytic-like effect of neuropeptide Y, while the Y2 receptor antagonist was ineffective.We conclude that neuropeptide Y in the dorsocaudal lateral septum may act as an endogenous anxiolytic and antagonize corticotropin-releasing hormone (stress)-induced anxiety. This functional antagonism probably shapes behavior under aversive conditions, as neuropeptide Y-induced anxiolysis is not tonic in nature. An imbalance between these two neuropeptide systems in the septum may lead to a maladaptive expression of anxiety after stress exposure.
Kask
A
A
Department of Pharmacology, University of Taru, Estonia.
Nguyen
H P
HP
Pabst
R
R
Von Hörsten
S
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D003346:Corticotropin-Releasing Hormone