Cocaine- and amphetamine-regulated transcript peptide produces anxiety-like behavior in rodents.
Cocaine- and amphetamine-regulated transcript (CART) peptide (CART-(55-102)) is involved in the suppression of food intake. We now report that CART-(55-102) is involved in anxiety in rodents. Intracerebroventricularly administered CART-(55-102) as well as intraperitoneal administration of N-methyl-beta-carboline-3-carboxamide (FG-7142), a selective GABA(A)/benzodiazepine receptor inverse agonist, reduced time spent in the open arms in the elevated plus-maze task in mice. CART-(55-102)-induced anxiogenic-like behavior in this task was attenuated by widely prescribed anxiolytics such as diazepam and buspirone. Likewise, CART-(55-102) and FG-7142 significantly reduced social interaction in mice. Both diazepam and buspirone significantly reversed CART-(55-102)-induced anxiogenic-like behavior in social interaction tests. By contrast, another biologically active CART peptide, CART-(62-102), was without effect in the elevated plus-maze task in mice. Moreover, intracerebroventricular administration of CART-(55-102) markedly increased the firing rate of locus coeruleus neurons in single unit recording in anesthetized rats. As CART-(55-102) produced anxiety-like effects in rodents, this peptide may possibly be involved in anxiety and stress-related behavior.
Chaki
Shigeyuki
S
Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Saitama 330-8530, Saitama, Japan. s.chaki@po.rd.taisho.co.jp
Kawashima
Naoya
N
Suzuki
Yoshiko
Y
Shimazaki
Toshiharu
T
Okuyama
Shigeru
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D012919:Social Behavior; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D014151:Anti-Anxiety Agents; D002243:Carbolines; D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); C035874:FG 7142; D003975:Diazepam