Effect of MS-153 on the acquisition and expression of conditioned fear in rats.
Pavlovian fear conditioning is one of the most extensively studied and reliable behavioral paradigms used to investigate the mechanisms involved in fear and anxiety. Increased glutamatergic neurotransmission may play an important role in mediating fear conditioning. The present study assessed whether (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a novel cerebroprotective agent that inhibits the release of glutamate and enhances glutamate uptake, affects the acquisition and expression of conditioned fear. The rats received administration of MS-153 (i.p.) at 3, 10, and 30 mg/kg, 30 min before footshock and 24 h after footshock. Freezing behavior was measured in the chamber where they had previously received footshock for the acquisition experiments. For the expression experiments, the rats received MS-153 (i.p.) at the same doses 23.5 h after footshock and 30 min before expression testing. MS-153 significantly attenuated the acquisition and expression of freezing behavior. In addition, MS-153 administration did not affect locomotor activity. The present results suggest that extracellular glutamate is involved in fear conditioning, and that MS-153 has an anxiolytic effect by decreasing endogenous glutamate neurotransmission.
Li
XiaoBai
X
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan. xiao@med.hokudai.ac.jp
Inouei
Takeshi
T
Abekawai
Tomohiro
T
YiRui
Fang
F
Koyama
Tsukasa
T
D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009539:Nicotinic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C101692:5-methyl-1-nicotinoyl-2-pyrazoline; D009539:Nicotinic Acids