Modulation of the effects on learning and memory of nootropic drugs and central stimulants when applied together

In experiments on rats using passive avoidance with punishment reinforcement (step-through) and two-way active avoidance with punishment reinforcement (shuttle-box), we examined the effects on acquisition and retention of different combinations of the nootropic drugs meclofenoxate (Mf), citicholine (CCh), piracetam (Pc), the structural analogues of aniracetam p-P and p-F, standardized extract from ginseng roots (PG) and the psychostimulants caffeine (Caf) and amphetamine (Amph). Favorable effects (more pronounced improvement of learning and/or memory as compared to that caused by the drugs when given alone) were in some cases obtained by the combination Mf+Caf, Pc+Caf, CCh+Caf, p-F+Caf, Mf+CCh, as well as by the combination Mf+PG applied to rats with electroconvulsive shock-induced amnesia. However, in some cases the combined administration of two drugs with favorable effects on memory did not led to summation or potentiation but rather to disappearance of these effects. This was observed under certain experimental conditions with some combinations of Caf and CCh, Mf, Pc and p-P and with some combinations of Amph and Mf. Based on our earlier results and data in the literature, we present some considerations about the role of the neurotransmitter mechanisms of action of the drugs tested as neurochemical correlates of their effects on memory. It is suggested that the unfavorable results obtained in some cases with combinations of nootropics and psychostimulants are due to the possible disturbance of selective acquisition by the psychostimulant drug.