Disinhibitory effects of LY354740, a new mGluR2 agonist, on behaviors suppressed by electric shock in rats and pigeons

Abstract

Compounds which affect glutamate transmission are reported as anxiolytic in a number of animal models. In the present studies, we evaluated the anxiolytic effect of a new mGluR2 agonist, LY354740, in rats and pigeons. LY354740 was evaluated in three different rat punished responding assays, using different levels of shock intensity. LY354740 and its racemate, LY314582, were generally ineffective at increasing rates of responding suppressed by electric shock. However, both compounds did increase responding during time-out periods between scheduled components, and both increased responding during a punishment extinction assay. LY354740 was also evaluated in two separate pigeon punished responding procedures. LY354740 was ineffective at increasing punished responding under one schedule, but increased punished responding in the second assay, when shock was not delivered coincident with reinforcement. Clearly, LY354740 was effective in attenuating suppressed responding in some cases, but not all. LY354740 appears to produce a disinhibitory effect on behaviors with low baseline rates of responding (in rats), and a disinhibitory effect on punished behaviors in schedules with less stringent punishment conditions (in rats and pigeons). These results suggest that LY354740 may be useful as a clinically effective anxiolytic. Drug Dev. Res. 47:37–44, 1999. © 1999 Wiley-Liss, Inc.