Abstract
Recent progress in understanding molecular and cellular mechanisms of conditioning make it timely to reevaluate interfaces between well-defined unitary cellular mechanisms and subtle, complex, multifactorial animal behaviors. The purpose of this chapter is to call attention to two robust phenomena observed during studies of the behavioral pharmacology of memory. We consider these phenomena to provide interesting possibilities for exploration at the cellular level. The first phenomenon is that pharmacological probes of memory in living organisms can have opposite effects. That is to say, a given drug in a given experimental paradigm can either enhance or impair memory, depending on dose. The second phenomenon is that several two-drug combinations exhibit powerful supraadditivity (as much as 20-fold) of memory-enhancing potency. The question is, can molecular and cellular approaches help to explain these two phenomena? The interfaces involve multiple interactions and functional linkages (Schmitt and Schneider, 1975). Atkinson (1975) has pointed out:
Any discussion of biological processes must always involve oversimplification, because bio-molecular reactions are always part of a larger whole. Biomolecular processes may be of some interest in their own right, but their biological significance relates to their effects on a larger system.
The black box approach, in which the intermediate mechanisms between a stimulus and its induced response are not considered, can lead, and has led, to much useful information in physiology and biophysics. It poses questions that a mechanistically oriented approach can then be used to resolve. However, this approach is limited and in a sense outmoded.
In contrast, biochemists deal with small portions of large systems and frequently become so intrigued with the properties of these parts that they forget that they are, in situ, functioning elements within a complex interacting system....
These two basic approaches must be combined in order to obtain information that is biologically meaningful. Every aspect of an organism is designed by mutation and selection, but we must remember that while it is molecular detail that mutates, it is overall organismic function that is selected. Both the molecular and the black-box approaches must be used, but the area of real interest is in the linkage between them, the ways in which molecular detail is responsible for the overall response or for the living functioning organism.
Dosis toxinum facit.
Paracelsus
When we try to pick out anything by itself, we find it hitched to everything else in the universe.
John Muir
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Cherkin, A., Flood, J.F. (1988). Behavioral Pharmacology of Memory. In: Woody, C.D., Alkon, D.L., McGaugh, J.L. (eds) Cellular Mechanisms of Conditioning and Behavioral Plasticity. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9610-0_32
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