Learning and Memory Enhancement by Drugs which Indirectly Promote Cholinergic Neurotransmission
Brain cholinergic functions severely decline in Alzheimer (AD) patients. This conclusion is based upon many studies of biopsy samples as well as postmortem analyses of brain areas of AD patients. Alzheimer’s disease is usually characterized by marked reduction in markers of pre-synaptic cholinergic activity, including choline acetyl-transferase (ChAT), high affinity choline-uptake, and synthesis of acetylcholine (ACh). More recently, a reduction in brain content of choline was reported in cortical post-mortem samples from AD patients. Similarly, there is a correlation between AD and the tetrameric membrane bound or G4 form of acetylcholinesterase (AChE). A significant number of efforts are underway to design pharmacotherapeutic treatment of AD based upon the cholinergic deficit hypothesis. Based upon the present knowledge of the cholinergic pharmacology, several approaches are available. For example, any decline in cholinergic activity may be reversed by application of agonists of cholinergic receptors, inhibitors of AChE, agents that release ACh in the cholinergic synaptic cleft, and precursors which can be converted into choline. Not knowing for sure, which approach would be more effective, at present, all of these approaches are being researched to discover drugs which are efficacious in ameliorating AD. Whereas many of the cholinergic drugs show positive activity in the animal models of memory deficits, their efficacy in AD patients is not unimpressive and is not long lasting enough to be useful in providing a meaningful treatment of AD (for review, see Gamzu and Gracon, 1988; Retz and Lal, 1985).
KeywordsPlacebo Dementia Schizophrenia Neurol Choline
Unable to display preview. Download preview PDF.
- Drachman DA and Sahakian BJ (1979): Effects of cholinergic agents on human learning and memory. In: Nutrition and Brain, Barbeau A, Growdon JH and Wurtman RJ, eds. New York: Raven Press, pp. 351–365.Google Scholar
- Forster MJ and Lal H (1991): Neurobehavioral biomarkers of aging: Influence of genotype and dietary restriction. Biomedical and Environmental Sciences (In Press).Google Scholar
- Forster MJ and Lal H (1991): Autoimmunity and cognitive decline in aging and Alzheimer’s disease. In: Psychoneuroimmunology, Second Edition, Ader R, Cohen N and Feiten D, eds. New York: Academic Press, pp.709–748.Google Scholar
- Gamzu ER and Gracon SI (1988): Drug improvement of cognition: hope and reality. Psychiat Psychobiol 3:115–123.Google Scholar
- Lal H, Kumar BA and Forster MJ (1988): Enhancement of learning and memory in mice by a benzodiazepine antagonist. FASEB J 2:2707–2711.Google Scholar
- Prather PL, Forster MJ and Lal H (1991): Learning and memory enhancing effects of RO 15-4513: a comparison with flumazenil. Neuropharmacol (In Press).Google Scholar
- Rigdon GC and Pirch JH (1986): Nucleus basalis involvement in conditioned neuronal responses in rat frontal cortex. J Neurosci 6:2535–2542.Google Scholar
- Singh MM and Lal H (1982): Central cholinergic mechanisms, neuroleptic action and schizophrenia. In: Neuropharmacology: Clinical Application, Essman WB and Valzelli L, eds. New York: Spectrum Publications, pp. 337–389.Google Scholar