Hippocampal 5-HT(1A) Receptor and Spatial Learning and Memory

Spatial cognition is fundamental for survival in the topographically complex environments inhabited by humans and other animals. The hippocampus, which has a central role in spatial cognition, is characterized by high concentration of serotonin (5-hydroxytryptamine; 5-HT) receptor binding sites, particularly of the 1A receptor (5-HT(1A)) subtype. This review highlights converging evidence for the role of hippocampal 5-HT(1A) receptors in spatial learning and memory. We consider studies showing that activation or blockade of the 5-HT(1A) receptors using agonists or antagonists, respectively, lead to changes in spatial learning and memory. For example, pharmacological manipulation to induce 5-HT release, or to block 5-HT uptake, have indicated that increased extracellular 5-HT concentrations maintain or improve memory performance. In contrast, reduced levels of 5-HT have been shown to impair spatial memory. Furthermore, the lack of 5-HT(1A) receptor subtype in single gene knockout mice is specifically associated with spatial memory impairments. These findings, along with evidence from recent cognitive imaging studies using positron emission tomography (PET) with 5-HT(1A) receptor ligands, and studies of individual genetic variance in 5-HT(1A) receptor availability, strongly suggests that 5-HT, mediated by the 5-HT(1A) receptor subtype, plays a key role in spatial learning and memory.