The theoretical concepts short-term memory (STM) and working memory (WM) have been used to refer to the maintenance and the maintenance plus manipulation of information, respectively. Although they are conceptually different, the use of the terms STM and WM in literature is not always strict. STM and WM are different theoretical concepts that are assumed to reflect different cognitive functions. However, correlational studies have not been able to separate both constructs consistently and there is evidence for a large or even complete overlap. The emerging view from neurobiological studies is partly different, although there are conceptual problems troubling the interpretation of findings. In this regard, there is a crucial role for the tasks that are used to measure STM or WM (simple and complex span tasks, respectively) and for the cognitive load reflected by factors like attention and processing speed that may covary between and within these tasks. These conceptual issues are discussed based on several abstract models for the relation between STM and WM.

During the last decennia, our understanding of the neurobiological processes underlying learning and memory has continuously improved, leading to the identification of targets for the development of memory-enhancing drugs. Here we review a class of drugs which has more recently been identified: the phosphodiesterase (PDE) inhibitors. An overview is given of the different PDEs that are known and we focus on three PDEs which have been identified as possible relevant targets for memory improvement: PDE2, PDE4 and PDE5. PDEs differ in the substrate, i.e. cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP), being hydrolyzed. Since these cyclic nucleotides have been suggested to play distinct roles in processes of memory, selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. The present data suggest that PDE4 (cAMP) is involved in acquisition processes, although a possible role in late consolidation processes cannot be excluded. PDE5 (cGMP) is involved in early consolidation processes. Since PDE2 inhibition affects both cAMP and cGMP, PDE2 inhibitors may improve both memory processes. The field of PDEs is highly dynamic and new isoforms of PDEs are still being described. This may lead to the discovery and development of new memory enhancing drugs that selectively inhibit such isoforms. Such drugs may exert their effects only in specific brain areas and hence possess an improved side effect profile.

The tryptophan (TRP) depletion method has been used as a tool to investigate the effects of acute lowered serotonin levels in the brain. In the present study, the effects of this treatment were investigated in rat models of anxiety (open field test, home cage emergence test), depression (forced swimming test, sucrose preference test) and cognition (spatial discrimination learning, sustained attention). It was found that the repeated TRP depletion increased anxiety-related behaviour in the open field test and increased immobility in the forced swimming test. The other behavioural tests did not reveal effects of treatment. TRP levels were decreased in plasma (34%) and hippocampus (33%) but not in the cortex. Stress-induced corticosterone levels were not affected after TRP depletion. The present findings indicate that repeated moderate TRP depletion leads to anxiogenic and depressive-like behaviour in the rat and corroborates the notion of the involvement of serotonin in these behaviours.