The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 9 No.
3 • August 2006
Cognition-Enhancing Drugs May Work Exactly the Same in Rats as Environmental Enrichment
Three drugs that augment cholinergic function—tacrine (inhibits acetylcholinesterase), deprenyl (increases acetylcholine function indirectly via improved dopamine function), and nefiracetam (improves cholinergic function and increases neurite outgrowth)—as well as increasing NCAM PSA (neural cell adhesion molecule, polysialic acid expression), were tested in rats for mechanistic changes. The bottom line: the researchers found that these drugs all “increase the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing.”
As the authors explain, “[w]ithin the hippocampus, a transient increase in polysialylation of neurons located at the dentate infragranular zone at 10–12 hours following learning is necessary for memory consolidation. … This neuroplastic mechanism is required for dendritic remodeling and is likely to be an important factor in the elaboration and integration of circuitry associated with the consolidation of novel behavioral repertoires. … Moreover, reduced requirement for neuroplastic activation, improved maze learning, and increased resilience against cholinergic deficits accompany the enhanced NCAM [neural cell adhesion molecule] PSA [polysialic acid] expression in the hippocampus following drug or environmental interventions.” [Citations deleted from quotes]
As a combination of treatments (drug + environmental enrichment) did not further increase basal polysialylated cell frequency, they probably work via the same mechanism(s). Thus, the authors conclude, “[t]hese findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease-modifying action of drugs such as cholinesterase inhibitors.” (Galantamine, which we take, is a cholinesterase inhibitor that we would expect to function similarly to the cholinergic function-enhancing drugs tested in this study.)
The authors note that the frequency of the dentate polysialylated neurons declines markedly with age in both rodents and humans; hence the effects of a chronic, cholinergic function-enhancing drug or a complex environment “may relate to an attenuation in the decline of this cell population.”
- Murphy et al. Chronic exposure of rats to cognition-enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing. Neuropsychopharmacology 31:90-100 (2006).