Effects of modulation of NMDA neurotransmission on response rate and duration in a conflict procedure in rats.
N-Methyl-D-aspartate (NMDA) antagonists and gamma-aminobutyric acid agonists share a number of common pharmacological properties, including motor and anticonvulsant effects. In the present study, site-selective NMDA antagonists were evaluated for potential anxiolytic efficacy and motor impairment in a modified Geller-Seifter conflict procedure, an animal model widely used to screen drugs for anxiolytic effects. Male Sprague-Dawley rats were trained to respond for food reward under a multiple FI 30 s (food only), FR 10 (food + shock) operant schedule. Consistent with the results of previous studies, the benzodiazepines chlordiazepoxide and diazepam selectively increased punished responding and increased response durations at higher doses. The competitive NMDA antagonist CGP 37,849 increased punished responding at some doses, though not selectively, and also increased response duration in both schedule components. The glycine-site modulators milacemide, ACEA 1011 and ACEA 1021, the NR2B-selective polyamine site antagonist eliprodil and NMDA did not produce anticonflict effects at any dose and had inconsistent effects on response durations. These results suggest that the anticonflict effects of NMDA antagonists are not as reliable as those of the benzodiazepines. Further research is needed to clarify the experimental conditions under which the anxiolytic potential of NMDA antagonists is most evident.
Wiley
J L
JL
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298-0613, USA. jwiley@hsc.vcu.edu
Compton
A D
AD
Holcomb
J D
JD
McCallum
S E
SE
Varvel
S A
SA
Porter
J H
JH
Balster
R L
RL
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012201:Reward; D009435:Synaptic Transmission / Q000502:physiology*
D000081:Acetamides; D014151:Anti-Anxiety Agents; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C039332:milacemide; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; C082999:ACEA 1011; C092062:licostinel; D002707:Chlordiazepoxide; D015763:2-Amino-5-phosphonovalerate; D003975:Diazepam