The role of hippocampus in anxiety: intracerebral infusion studies.

Although current models of hippocampal function stress its well-known role in cognitive functions, historically it has also been viewed as a neural mediator of emotion. Here, we review recent evidence from intrahippocampal infusion studies in animals that support a distinctive role of the hippocampus in anxiety, independent of its roles in learning and memory. Specifically, gamma-aminobutyric acid type A receptor agonists, both direct and indirect, reliably inhibit a number of animals' untrained anxiety reactions when microinfused into the hippocampus, whereas gamma-aminobutyric acid type A receptor antagonists do not. Intrahippocampal infusions of glutamatergic, serotonergic and cholinergic compounds also produce statistically reliable antianxiety effects, but the results vary as a function of specific anxiety reactions, and to some extent specific intrahippocampal targets. One hypothesis that may accommodate some of this variability is that anxiety is functionally segregated within the hippocampus, with ventral subregions more involved in anxiety-related processes, and dorsal subregions more involved with cognitive processes. Another possibility is that different hippocampal functions (e.g. memory and anxiety) are mediated by different neurotransmitter systems and/or different receptor subtypes within the hippocampus. Although there is some evidence that supports the latter hypothesis, the evidence for the former is not conclusive. Overall, however, the data clearly suggest that the hippocampus is importantly and directly involved in the mediation of untrained anxiety reactions in animals.