Facilitation and inhibition of retrieval in two aversive tasks in rats by intrahippocampal infusion of agonists of specific glutamate metabotropic receptor subtypes

Rationale: The generic antagonist of glutamate metabotropic receptors (mGlu s), MCPG, blocks retrieval of inhibitory avoidance when infused into the CA I area of rat hippocampus. It was considered important to study the effect of agonists of different types of mGlus on retrieval both of this task and of a related one, contextual fear. Objectives: To measure the effect of thr ee mGlu agonists (3HPG, which is selective to mGlu(1); LCCG, which binds to mGlu(2) and mGlu(3); and LAP-4, which binds to mGlu(4) and mGlu(5)), infus ed bilaterally into CA I, on the retrieval of one-trial inhibitory avoidanc e and contextual fear in rats. Methods: Rats bilaterally implanted with can nulae in the CAI region of the dorsal hippocampus were trained in one-trial step-down inhibitory avoidance or in a contextual fear task and tested for retention 24 h later. The drugs 3HPG, LCCG and LAP-4 were infused into CAI at different concentration levels 10 min before retention testing. In addi tion, we studied the effect of these drugs on locomotor and exploratory act ivity measured in an open field, and on pro- and anticonflict behaviour in an elevated plus-maze. Results: 3HPG hindered, and LCCG and LAP-4 enhanced, retrieval of the two tasks. In all cases the effects were dose-dependent. The drugs had no effects on open field or plus maze behaviour. Conclusions: Retrieval of one-trial inhibitory avoidance and of contextual fear is regu lated by mGlus in the CA1area of the rat hippocampus. The results suggest t hat mGlu(2)s, mGlu(3)s, mGlu(4)s and mGlu(6)s are necessary for retrieval a nd that mGlu(1)s play an inhibitory role. The effects are not explainable b y nonspecific influences on locomotor or exploratory activity or anxiety le vels.