Effects on Learning and Memory

HA has been found to be an effective cognition enhancer in a broad range of animal cognitive models by Tang et and in clinical trials (see Section 4.4.3).  

The effects of HA on the dismption of spatial memory induced by the muscarinic antagonist scopolamine and (y-amino-n-butyric acid (GABA)) against muscimol in the passive avoidance task was tested in chicks. The avoidance rate was evaluated as memory retention. Both scopolamine (100 ng) and muscimol (50 ng), injected intracranially 5 minutes before training, resulted in a decreased avoidance rate. HA (25 ng), injected intracranially 15 minutes before training, reversed memory deficits 

Reserpine [0.1 mg/kg intramuscularly (i.m.)] or yohimbine (0.01 mg/kg i.m.) induces significant impairments in the monkey s ability to perform the delayed response task. HA at a dosage of 0.01 mg/kg i.m. for the yohimbine-treated monkeys markedly improved the memory impairments. The effects exhibited an inverted U-shaped dose-response pattern. The data suggest that HA may improve working memory via an adrenergic mechanism.  

It was reported that subchronic administration of HA did not induce deleterious effects on spatial memory in guinea pigs. A systematic comparison of tolerances between the mixed acetyl-butyryl-ChE inhibitors and the selective AChEls such as HA indicated that they showed a remarkably similar profile of behavioral symptoms associated with overdosing in rats.  

---

There is not a consensus about the procedures to use to test for effects on learning and memory. The two most commonly used techniques are the water-filled maze, which is preferred for measuring learning, and passive avoidance, which is preferred for measuring memory (see Buelke-Sam et al., 1985). Retention is tested in a repeat test conducted approximately 1 week later. 

Neurotoxicity has been extensively studied in developing mice and rats that were exposed to aluminum during gestation, lactation, and/or directly via diet following weaning. As summarized in Section 2.2.2.6, effects on reflexes and simple motor behaviors were commonly found in aluminum-exposed developing animals, whereas effects on learning and memory have not been consistently shown. 

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... 

Cognitive function can be impaired by fluoxetine a negative effect on learning and memory has been described (SEDA-17, 20). 

Vasopressin nay serve as the precursor of smaller molecules with effects on learning and memory. The cycllzed derivative of the C-term-Inal dipeptlde of arginine vasopressin (cyclo-(Arg-Gly)) was found to block puromycin-induced amnesia in mlce. The C-terminal tripeptlde of oxytocin (L-prolyl-L-leucyl-glyclneamide or PLG) has been reported to cause an enhancement of memory in chicks. 

Biosynthesis The biosynthesis of the L. a. has not been completely elucidated. Since Lycopodium species cannot or can only be cultivated with difficulty, tracer experiments must be performed at the natural locations. It is certain that the biogenetic building blocks for the complex ring systems are lysine and acetate. Pharmacological activity The L. a. are moderately toxic. Some L. a. are purported to be potent inhibitors of acetylcholine esterase. Huperzine A has attracted attention on account of its stimulating effect on learning and memory behavior in laboratory animals. In Chinese traditional medicine various Lycopodium species are used to treat skin diseases and as a tonic. 

One of the simplest procedures for looking for adverse effects on learning and memory is the so-called one-trial passive avoidance task [15]. There are several variants of this procedure, but the basic principal is that a rat or a mouse receives an aversive stimulation in the recognizable environment and on a later occasion shows it has remembered by not going there (passive avoidance). For example, a rat placed into the lit compartment of a two-compartment box will explore the apparatus and eventually enter... 

---