The first study below finds that very-high doses of melatonin produced dose-dependent short-term memory deficits possibly via the same mechanism that Valium-class drugs (benzodiazepines) impair memory. The doses were equal to .6 to 6.8 grams for a 150-lb subject, very high! Interestingly, and fortunately for melatonin consumers, the second and third studies below found that endogenous melatonin and exogenous doses of melatonin in the standard-dose-range actually facilitated memory. The forth study supports the hypothesis that melatonin may be beneficial in the treatment of Alzheimer's disease in part by reducing the accumulation of beta-amyloid.
Evidence of GABAergic modulation in melatonin-induced short-term memory deficits and food consumption.
Shaji AV, Kulkarni SK
Pharmacology Division, Panjab University, Chandigarh, India.
Many of the pharmacological effects of melatonin
have been found to be similar to those of
benzodiazepines. In the present study, we analyzed
the role of melatonin on short-term memory retrieval
on transfer latency in elevated plus maze and food
consumption behavior, and the effects were compared
with those of diazepam. Melatonin dose-dependently
(10-100 mg/kg) produced short-term memory deficit
and it potentiated diazepam- (1 mg/kg) induced cognitive deficit in mice. Flumazenil (1 and 4 mg/kg) could reverse enhancement in diazepam-induced memory deficit by melatonin. Chronic treatment with melatonin
(10 mg/kg/7d) produced a similar profile in transfer
latency on elevated plus maze compared with that of diazepam. In a food consumption behavior study, melatonin (25 and 50 mg/kg) produced a significant hyperphagic effect compared to control. Flumazenil
(4 mg/kg) could significantly reverse the hyperphagic
effects induced by diazepam (2 mg/kg), but would be insignificant with regard to that due to melatonin. These findings provide further evidence that some of the pharmacological effects of melatonin are comparable with those of diazepam and may involve central GABAergic mechanism.
Melatonin facilitates short-term memory.
Argyriou A, Prast H, Philippu A
Department of Pharmacology and Toxicology, University of Innsbruck, Austria.
The olfactory social memory test, based on the
recognition of a juvenile rat by a male adult
rat, was used to investigate whether melatonin
influences memory. Intracerebroventricular
(i.c.v.) injection of 1.1 nmol melatonin
shortened recognition time, while the melatonin ML1 receptor antagonist luzindole (1 nmol) exerted the opposite effect. The facilitating influence of melatonin was abolished in the presence of 0.5 nmol luzindole. The findings suggest that endogenous melatonin facilitates short-term memory.
Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment.
Jean-Louis G, von Gizycki H, Zizi F
Department of Psychiatry, University of California, San Diego, USA. firstname.lastname@example.org
The effects of immediate-release melatonin on circadian rest-activity profiles, cognition, and mood were investigated in ten elderly individuals with self-reported sleep-wake disturbances. Melatonin (6 mg), administered 2 hr before habitual bedtime, enhanced the rest-activity rhythm and improved sleep quality as observed in a reduction in sleep onset latency and in the number of transitions from sleep to wakefulness. However, total sleep time was not significantly increased nor was wake within sleep significantly reduced. The ability to remember previously learned items improved along with a significant reduction in depressed moods. No side effects or contraindications were reported by any of our participants during the 10 day trials. These data suggest that melatonin can safely improve some aspects of sleep, memory, and mood in the elderly in short-term use.
ABSTRACT: Monozygotic twins with Alzheimer's disease
of 8 years duration were studied. The onset of the
disease differed by about 6 months between twins and
was characterized by a primary impairment of memory
function. Clinical evaluation at the time of diagnosis
indicated a similar cognitive and neuroimaging alteration
in both patients, as well as a similar neuropsychologic
impairment. A possible genetic origin of the disease was
suggested by a similar disease suffered by the mother.
Patients were initially treated with vitamin E
(800 I.U./day). Starting at approximately the same time
(about 3 years ago), they received 50 mg/day thioridazine
because of the behavioral and sleep disorder. One of the patients was treated with melatonin (6 mg orally) at bed time daily for 36 months. Evolution of the disease in the melatonin-treated patient indicated a milder impairment of memory function, with substantial improvement of sleep quality and reduction of sundowning. This led to discontinuance (after 3 months) of thioridazine treatment. Present clinical evaluation indicated a difference in functional stage of the disease between the twins
(Functional Assessment Tool For Alzheimer's Disease,
FAST), with a score of 5 in the twin who received melatonin and of 7b in the twin who did not receive it. Since experimental data on melatonin in animals indicated its antioxidant, antiapoptotic, and beta-amyloid-decreasing activity, the hypothesis that melatonin has a beneficial effect in Alzheimer's disease patients should be considered.
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