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

Compounds which affect glutamate transmission are reported as anxiolytic in a number of animal models. in the present studies, we evaluated the anxiol ytic effect of a new mGluR2 agonist, LY354740, in rats and pigeons. LY35474 0 was evaluated in three different rat punished responding assays, using di fferent levels of shock intensity. LY354740 and its racemate, LY314582, wer e generally ineffective at increasing rates of responding suppressed by ele ctric shock. However, both compounds did increase responding during time-ou t periods between scheduled components, and both increased responding durin g a punishment extinction assay. LY354740 was also evaluated in two separat e pigeon punished responding procedures. LY354740 was ineffective at increa sing punished responding under one schedule, but increased punished respond ing in the second assay, when shock was not delivered coincident with reinf orcement. Clearly, LY354740 was effective in attenuating suppressed respond ing 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 stringen t punishment conditions (in rats and pigeons). These results suggest that L Y354740 may be useful as a clinically effective anxiolytic. (C) 1999 Wiley- Liss, Inc.