Memory and learning

A number of different tests have been used for assessing effects on learning and memory. Many of these are based on the animals moving and using their senses therefore, an impaired performance in a learning test may reflect behavioural effects other than learning 

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Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

AVP is excitatory in the ventral hippocampus, either directly or by potentiation of glutamatergic responses. An inhibitory effect has been observed in AVP may be involved in the formation of long-term potentiation and thus learning and memory. However, AVP is proconvulsive, may augment the formation of dmg tolerance and dependence, and affects cardiovascular regulatory processes. 

The combination of meclofenoxate [51-68-3] and citicoline [987-78-0] h.2is been reported to enhance learning and memory retention in aged rats (22). 

CaM plays a key role in many cellular processes. In the CNS, it is involved in synaptic transmission and neuronal plasticity associated with short-term and longterm potentiation, and learning and memory processes. 

Within the nervous system, ChEs were shown to be involved in membrane conductance and transmission of excitatory amino acids, learning and memory, neurite growth, neuritic translocation and acute stress reactions. Recent findings propose AChE s involvement in apoptosome formation [2]. 

PKC isozymes are involved in a wide array of diverse cellular functions [5]. Most isozymes (e.g., PKC (3) are involved in proliferative responses, and hyperactivation with phorbol esters most typically results in cell growth and differentiation. However, isozymes can have opposing functions. PKC 8 is well-characterized as an apoptotic kinase, whereas the closely related PKC e is antiapoptotic. PKC also plays a key role in learning and memory. 

S100B Developmental brain dysfunction, learning and memory deficits... 

Wernicke s syndrome is a serious consequence of alcoholism and thiamine (vitamin Bx) deficiency. Certain characteristic signs of this disease, notably ophtalmoplegia, nystagmus, and ataxia, respond rapidly to the administration of thiamine but to no other-vitamin. Wernicke s syndrome may be accompanied by an acute global confusional state that may also respond to thiamine. Left untreated, Wernicke s syndrome frequently leads to a chronic disorder in which learning and memory are strongly impaired. This so-called Korsakoff s psychosis is characterized by confabulation, and is less likely to be reversible once established. 

Venault P, Chapouthier G, de Carvalho LP, et al Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks. Natme 321 864-866, 1986... 

George J, Andrade C, Joseph T. 1992. Delayed effects of acute oral and chronic inhalational exposure to methyl parathion on learning and memory in rats. Indian J Exp Biol 30 819-822. 

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

NMDAR. An ionotropic receptor for glutamate. It plays a critical role in synaptic plasticity mechanisms and thus is necessary for several types of learning and memory. 

Although there is no evidence that the neuronal degeneration of AzD results, as in cardiovascular ischaemia, from the excitotoxicity of increased intracellular Ca +, some calcium channel blockers have been tried in AzD. They have had little effect but surprisingly a pyrrolidone derivative nefiracetam, which opens L-type voltage-sensitive calcium channels (VSCCs) reduces both scopolamine- and )S-amyloid-induced impairments of learning and memory in rats (Yamada et al. 1999). This effect can be overcome by VSCC antagonists, but nefiracetam has not been tried in humans. 

McGough, JL, Introlni-Collison, IB and Castellano, C (1993) Involvement of opioid peptides in learning and memory. In Opioids II. Handbook of Experimental Pharmacology, Springer-Verlag, New York, pp. 429—448. 

Yamada, K, Tanaka, T, Mamiya, T, Shiotani, T, Kameyama, T and Nabeshima, T (1999) Improvement by nefiracetam of /i-amyloid—(1-42)—induced learning and memory impairments in rats. Brit. J. Pharmacol. 126 235-244. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

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