SSR504734, a glycine transporter-1 inhibitor, attenuates acquisition and expression of contextual conditioned fear in rats.
Conditioned stress-induced freezing has been used as an indicator of anxiety in rodents to evaluate the anxiolytic effects of various compounds. However, the role of glycinergic neurotransmission in fear conditioning is not well understood. In this study, we investigated the effects of a selective glycine transporter-1 inhibitor, SSR504734, on contextual fear conditioning. In a fear acquisition experiment, rats were administered SSR504734 (3-30 mg/kg, intraperitoneal) 1 h before fear conditioning (i.e. inescapable footshock). Twenty-four hours after fear conditioning, the rats were placed in the experimental chamber without footshock, and freezing behavior was observed. SSR504734 (30 mg/kg) significantly inhibited contextual conditioned freezing. In a fear expression experiment, rats were administered SSR504734 (3-30 mg/kg, intraperitoneal) 23 h after fear conditioning and were tested 1 h after injection. SSR504734 (30 mg/kg) significantly inhibited contextual conditioned freezing. These findings indicate that SSR504734 attenuates both the acquisition and expression of contextual conditioned fear, and suggest that glycinergic neurotransmission may play an important role in conditioned fear.
Nishikawa
Hiroyuki
H
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Inoue
Takeshi
T
Izumi
Takeshi
T
Nakagawa
Shin
S
Koyama
Tsukasa
T
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D005615:Freezing; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C507205:2-chloro-N-((S)-phenyl((2S)-piperidin-2-yl)methyl)-3-trifluoromethyl benzamide; D001549:Benzamides; D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines