Psychopharmacology of memory modulation: evidence for multiple interaction among neurotransmitters and hormones

Experimental results are reviewed which indicate that memory storage can be altered by a number of post-training treatments that affect different hormones and neurotransmitters. Moreover, evidence was reported which suggests that the action of treatments effective on memory processes involves interactions among different systems, consistently with the complexity of brain systems. In the last decade, inbred strains have been exploited to investigate the role of neurotransmitter and hormone systems in learning and memory, leading to behavioural and neurochemical correlations based on strain differences that provide unique information on the biological systems underlying behaviour. Research carried out on the inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA), demonstrates that the genetic makeup plays an important role in modulating response to drug administration. Thus, recent results have shown that in C57 mice, similarly to what occurs in outbred strains of mice or in rats, GABAergic agonists impair memory and antagonists improve it, whilst the opposite is evident in the DBA strain. By contrast, post-training administration of selective D1 or D2 agonists impairs and post-training administration of selective antagonists improves retention in DBA mice, whilst these agents have opposite effects in the C57 strain. Dose- and strain-dependent effects are evident also following post-training corticosterone as well as opioid agonists and antagonists administration. On the other side, these two strains react similarly to oxotremorine (improvement) and to atropine (impairment) administration, DBA mice being more responsive to the effects of both drugs than C57 mice. Data on the interactions between agents acting upon different neurotransmitter and/or hormonal systems in these strains indicate strain-dependent synergistic or antagonistic interactions among some of these systems, pointing to inbred strains of mice as an important methodological tool in the study of neural and hormonal factors involved in emotion and in its effects on cognition. In particular, these studies have been carried out on inbred strains of mice from which recombinant inbred (RI) strains are available that have recently been proposed as a choice experimental method in psychopharmacogenetics.