Use of behavioural and long-term potentiation models in the development of memory-improving drugs

Background: There is a great need to develop memory-enhancing drugs for the treatment of memory dysfunctions. Although many targets have been identified in preclinical studies, the number of clinically effective drugs is limited. Objective: In this overview, the relation between drug effects on hippocampal long-term potentiation (LTP) and memory-enhancing effects is explored for drugs that modulate cholinergic or glutamatergic neurotransmission or inhibit cyclic nucleotide metabolism. Methods: We limited our analysis to drug targets that are in clinical use or in development for the treatment of cognitive deficits and that have been tested in LTP. Results/conclusion: Although these drugs have been shown to improve in vitro or in vivo LTP and memory performance in many different models, no clear correlation between positive effects in LTP and behavioural assays is possible. The effectiveness in behavioural models is based on various models assessing different aspects of cognition. More uniformity in the use of behavioural tests is encouraged to better understand drug effects on different memory processes (i.e., acquisition, consolidation and retrieval). The systematic use of in vitro models such as LTP improves our understanding of the molecular mechanism of drug efficacy. This may lead to a better selection of models relevant to the specific cognitive processes disrupted in different pathological conditions and a more differentiated development of memory-enhancing drugs.