The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl- d-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus

Abstract

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl- d-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 μg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 μg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 μg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.