Antipsychotic-like effect of the AMPA receptor antagonist LY326325 as indicated by suppression of conditioned avoidance response in the rat.
The effect of LY326325, a novel AMPA receptor antagonist, on the conditioned avoidance response and catalepsy was investigated in the rat. The conditioned avoidance response is a behavioral methodology which is regarded to predict potential antipsychotic efficacy of experimental drugs. Catalepsy ratings were utilized to assess the putative propensity of LY325326 to induce extrapyramidal side effects. Systemic administration of LY326325, 18 mg/kg subcutaneously, caused a selective suppression of conditioned avoidance response, without effect on escape behavior or intertrial crosses. In addition, no catalepsy was observed. Our present and previous results support an antipsychotic effect of AMPA receptor antagonists with a low liability for extrapyramidal side effects, i.e. pharmacological effects consonant with an atypical antipsychotic profile.
Mathé
J M
JM
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Fagerquist
M V
MV
Svensson
T H
TH
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D003213:Conditioning, Psychological / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000494:pharmacology*
D007546:Isoquinolines; D018091:Receptors, AMPA; D013777:Tetrazoles; C082309:tezampanel