Chronic lithium treatment magnifies learning in rats.
rs1...@yahoo.com
Chronic lithium treatment magnifies learning in rats.
Nocjar C, Hammonds MD, Shim SS.
Department of Psychiatry, Louis Stokes Cleveland VA Medical Center,
Cleveland, OH 44141, USA; Department of Psychiatry, Case Western
Reserve University School of Medicine, Cleveland, OH 44106, USA.
Recent electrophysiological work shows that chronic lithium treatment
increases long-term potentiation (LTP) in neurons of the hippocampus,
and LTP is thought to be the major neurophysiological basis for the
development of learning and memory. This suggests that lithium might
enhance learning and memory. Available studies have mainly assessed
memory using aversive conditioning paradigms, but very little is
available on the effect of lithium on learning. Since lithium may
diminish anxiety or negative affect in adult rats, which would hinder
aversive learning, the present study used three different positive
reinforcement spatial cognitive tasks to determine whether chronic
lithium affects learning. Each task differed in complexity, in the
type of learning required, and in the reward received. For 4 weeks
prior to, and throughout all learning assessments, rats had continual
access to lithium chow or to a control chow diet. After 4 weeks'
access to their designated chow diet, rats began conditioning in the
hole-board spatial discrimination or T-maze delayed alternation tasks
in a counterbalanced fashion. They immediately began conditioning in
the opposite task once completing the first. This was then followed
with social place-preference conditioning, after 24-h isolation from
their home-cage social partner. Chronic lithium increased learning in
all three paradigms, regardless of the reward received. Indeed, both
food and social interaction supported enhanced learning. Thus the
learning effect was not merely due to an effect of lithium on food
palatability. Importantly, clinically relevant serum lithium levels
were evidenced at the time of testing. Lithium also marginally
enhanced memory as well. Thus chronic lithium treatment may improve
learning and memory in Alzheimer's disease, and do so not only by
blocking the formation of beta-amyloid and neurofibrillary tangles as
suggested by previous research, but also by enhancing mechanisms
involved in basal learning and memory formation, such as hippocampal
synaptic plasticity.
PMID: 17996377 [PubMed - as supplied by publisher]
Thomas Carter
Hi RS,
This is an interesting short term rat study. I've seen others that
support it. But for medical decisions human studies must be used
whenever possible. Here are just two of dozens that I have reporting
detrimental effects of lithium.
Thomas
(66) J Affect Disord. 2000 Nov;60(3):147-57. Related Articles, Links
A double-blind, placebo-controlled study of the effects of lithium on
cognition in healthy subjects: mild and selective effects on learning.
Stip E, Dufresne J, Lussier I, Yatham L.
Centre de Recherche Fernand Seguin, Hopital L.H. Lafontaine,
Universit? de Montr?al, 7331 Hochelaga, Qu?bec H1N 3V2, Montr?al,
Canada. emmanu...@umontreal.ca
BACKGROUND: Several studies have shown cognitive
impairment in short-term memory, long-term memory and psychomotor
speed in bipolar patients taking lithium. The aim of the study was to
look at the effect of lithium in normal subjects (N=30) taking lithium
for 3 weeks. A comprehensive battery was used to assess attention and
memory. METHODS: Subjects were randomized to double-blind treatment
with either lithium (N=15) or placebo (N=15) for a 3-week period.
Thirteen participants in the lithium group and 15 in the placebo group
completed the study. The lithium and placebo were administered twice
daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The
initial daily dose was calculated according to the Pepin formula to
achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive
performance (attention, memory) was assessed in each subjects during
three periods, i.e. at baseline, after 3 weeks of lithium or placebo,
and 2 weeks after discontinuation of study medication. RESULTS: In
short-term memory tasks, the performance of subjects in the lithium
group was worst 3 weeks after lithium treatment compared to 2 weeks
after discontinuation. In long-term memory, a significantly higher
number of words was recalled by the placebo group but not the lithium
group. CONCLUSIONS: Lithium may have an effect on learning when long-
term explicit memory test are administered repeatedly. It means that
the practice effect when a subject performs the same task several
times is less in the lithium-treated group than in the placebo group.
This practice effect is related to the learning of a task.
PMID: 11074103 [This was a hi lithium dose, and the authors for some
reason have failed to report between group comparisons.]
(68) Alzheimer Dis Assoc Disord. 2005 Jan-Mar;19(1):20-2. Related
Articles, Links
Does lithium therapy protect against the onset of dementia?
Dunn N, Holmes C, Mullee M.
Primary Medical Care, University of Southampton, Southampton, UK.
nick...@soton.ac.uk
Lithium compounds might theoretically play a role in
preventing dementia by inhibiting formation both of beta amyloid and
hyper phosphorylated tau protein. We carried out a case-control study
to assess any possible clinical effects of lithium therapy on the
diagnosis of dementia, using data from the General Practice Research
Database, which collects routine data from primary care patients in
the UK. Patients who received lithium had a higher risk of a diagnosis
of dementia compared with those who did not (adjusted odds ratio 1.8,
95% CI 1.1-2.8). There was a trend toward increasing risk with
increasing numbers of lithium prescriptions. This evidence does not
support the use of lithium for preventing dementia. PMID: 15764867
Kitty Antonik Wakfer
> On Nov 13, 3:00?pm, "rs10...@yahoo.com" <rs10...@yahoo.com> wrote:
>
<snip of original abstract>
>
> Hi RS,
>
> This is an interesting short term rat study. I've seen others that
> support it. But for medical decisions human studies must be used
> whenever possible. Here are just two of dozens that I have reporting
> detrimental effects of lithium.
>
> Thomas
<snip of Thomas' posted abstracts>
Thomas, these human studies you have brought forward are all using
high doses of lithium. I have taken both moderately high and low doses
of lithium carbonate, having been diagnosed with bipolar disorder back
in 1991 (I had an episode in late 1975 that was not then recognized as
BPD). During the peak of each of 4 manic episodes dating from 1991, I
was on 600 to 800 mg of lithium carbonate daily. Once the mania was
well subsiding (coinciding with hospital discharge for the first 3) I
was prescribed initially 100 mg lithium carbonate QID (4 times daily);
150 mg li carb TID (3 times daily) for the last one in 2003 when in
Canada, during which I was cared for at home by Paul. Every time when
my mania had passed I found that amount of lithium to be mentally
staggering, like trying to move through quicksand. Trying to function
at work (when employed prior to 8/2000 or with MoreLife.org in the
last episode) or driving a car was a terrible effort of concentration
(I don't think I could have responded quickly if needed behind the
wheel); my mind wanted to drop off into sleep. The psychiatrists were
cooperative about reducing the dosage from QID to TID and then after a
few months to BID. However, I still found at the BID level (300 mg
daily) that my thinking was not crisp and quick as it had been in the
year or 2 prior to each manic episode. Each of the times prior to the
2003 episode I had weaned myself slowly off the lithium wanting to
return to the mental clarity I was lacking; I was not aware of the
additional cognitive benefits from a small amount of lithium. (Work
pressures and the sudden death of my father lead to the 1991 episode;
work pressures and a less than happy marital relationship precipitated
the next 2 episodes.) I was down to 100mg every 3 days late 2002 and
because of study results indicating negative kidney and high
homocysteine effects, I and Paul decided I would stop the lithium. In
September of 2003 following several days of poor sleep due to
construction right outside our apartment and a sinus cold plus a red-
eye transatlantic flight followed by an enormously mentally
stimulating conference in UK and I was headlong into mania which Paul
was unable to stop with the chemicals available to him there. (Much
explanation and discussion of this episode is available at
MoreLife.org and MoreLife Yahoo.)
Since April 2004 for me and August of that year for Paul, we have been
taking 150mg lithium carbonate every 3 days. My mental clarity is
excellent - actually improved I think from my engineering days at
Motorola between 1/1984 and 8/2000 - as is my ability to sleep.
Probably 3 times in these past 3 years I have felt a slight hint of
hypomania and in each time I've taken a modestly increased amount of
some of our pre-sleep preparations for a day or 2; the first 2 times I
also took a lithium daily for 3 or 4 days. The last time I simply used
some of the techniques of cognitive therapy and by identifying the
stressor(s) I could modify my reactions to them without additional
lithium.
Paul could describe his own experience with low dose lithium. I will
simply say that I think it has helped to positively moderate his mood
swings, and it certainly has not reduced his mentally acuity.
So the point is, Thomas, low dose lithium (100 - 150mg lithium
carbonate every 3 days) is a completely different kettle of fish from
high doses - 600 mg lithium carbonate and more daily.
--
**Kitty Antonik Wakfer
MoreLife for the rational - http://morelife.org
Reality based tools for more life in quantity and quality
Self-Sovereign Individual Project - http://selfsip.org
Self-sovereignty, rational pursuit of optimal lifetime happiness,
individual responsibility, social preferencing & social contracting