Monoamine oxidase inhibitor and Morris water navigation task: Difference between pages

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In [[neuroscience]], the '''Morris water maze''' is a behavioral procedure designed to test [[spatial memory]]. It was developed by [[neuroscientist]] [[Richard Morris]] in [[1981]], and is commonly used today to explore the role of the [[hippocampus]] in the formation of [[spatial memory|spatial memories]].

'''Monoamine oxidase inhibitors''' ('''MAOIs''') are a class of [[antidepressant]] [[drug]]s prescribed for the treatment of [[clinical depression|depression]]. Due to potentially serious dietary and drug interactions they are used less frequently than other classes of antidepressant drugs (for example [[tricyclic antidepressants]] and [[selective serotonin reuptake inhibitor|selective serotonin reuptake inhibitors]]). However, in some cases where patients are unresponsive to other treatments they are tried, often with a marked success. They are particularly effective in treating [[clinical depression|atypical depression]], and have shown [[efficacy]] in helping smokers to quit.

== Overview ==

In the past they were prescribed for those resistant to [[tricyclic antidepressant]] therapy, but newer MAOIs are now sometimes used as first-line therapy. They are also used for treating [[agoraphobia]]. MAOIs, in their original form presented an unusual problem for the prescribing physician. If a physician was prescribing MAOIs for depression, he/she had to take into consideration the fact that he/she was offering the patient a ready, though unpleasant, route to suicide. Currently, the availability of [[Selegiline]] and [[moclobemide]] provides a safer alternative, although not always as effective as the old types. Additionally, studies suggest that the recommended dosage range for moclobemide (300-600mg) should be revised to 450mg-1200mg in major depression.

In the typical [[paradigm]], a [[rat]] or [[mouse]] is placed into a small pool of [[opaque]] water—back-end first to avoid [[stress (medicine)|stress]], and facing the pool-side to avoid bias—which contains a escape platform hidden a few [[millimeter]]s below the water surface. Visual cues, such as colored shapes, are placed around the pool in plain sight of the animal.

Transdermal delivery of deprenyl (20mg/day) has been tested, and the product is expected to be generally available some time in 2005. No dietary interactions have been observed with transdermal delivery, as intestinal MAO is not affected to a significant degree. The incidence of side effects was lower than that for placebo in all other categories than skin irritation at the application site (comparable to nicotine patches, about 1 in 3).

The pool is usually 4 to 6 feet in diameter and 2 feet deep. The pool could instead be half-filled with water at 1 foot deep. Some sidewall above the waterline prevents the rat from being distracted by lab activity. Mice are less cooperative in the water maze, but the bonus is that they are available as ‘knockout’ [[mutant]]s.

MAOIs act by inhibiting the activity of [[monoamine oxidase]] preventing the breakdown of monoamine [[neurotransmitter]]s and so increasing the available stores. There are two [[isoform]]s, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin and noradrenaline. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.

When released, the rat swims around the pool in search of an exit while various [[parameter]]s are recorded, including the time spent in each [[quadrant]] of the pool, the time taken to reach the platform ([[Latency (engineering)|latency]]), and total distance traveled. The rat's escape from the water reinforces its desire to quickly find the platform, and on subsequent trials (with the platform in the same position) the rat is able to locate the platform more rapidly. This improvement in performance occurs because the rat has learned where the hidden platform is located relative to the conspicuous visual cues. If the rat does not escape within 1 to 2 minutes, it is rescued. After enough practice, a capable rat can swim directly from any release point to the platform. This ability is attributed to a spatial map in a [[brain]] area called the [[hippocampus]].

MAOIs can potentiate the action of a number of other drugs, such as opiates, ephedrine, adrenaline, etc.

== Pharmacological manipulation ==

When ingested orally, they also inhibit the catabolism of dietary amines. Sufficient intestinal MAO-A inhibition can lead to hypertensive crises when foods containing [[tyramine]] are consumed, or [[hyperserotonemia]] if foods containing [[tryptophan]] are consumed. Hypertensive crises can sometimes result in stroke or cardiac arrythmia if not treated. This risk is not present with RIMAs. Both kinds of intestinal MAO-inhbition can cause [[hyperpyrexia]] if [[levodopa]]-containing foods are consumed.

Various [[drug]]s can be applied to test subjects before, during, or after maze training, which can reveal information about spatial learning and its underlying mechanisms. For example rats treated with the [[NMDA receptor]] blocker [[APV]] perform poorly in the Morris water maze, suggesting that NMDA receptors play a vital role in spatial learning [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1345945]. And since [[long-term potentiation]] -- a potential [[biology|biological]] mechanism for behavioral learning -- also requires NMDA receptors, spatial learning may require LTP.

Examples of foods with high levels of [[tyramine]] include [[liver]], [[Chianti]] and other aged [[wine]]s, aged [[cheese]]s, meat extracts (e.g. [[Bovril]]) and yeast extracts (e.g. [[Marmite]], [[Vegemite]]). Examples of levodopa-containing foods include [[Vicia faba|broad beans]].

Liang et al reported in [[1994]] that spatial learning requires both [[NMDA receptor|NMDA]] and [[AMPA receptor]]s, consolidation requires NMDA receptors, and the retrieval of spatial memories requires AMPA receptors [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7796636].

[[Tobacco]] and [[Harmal]] contain [[harmala]], which is an inhibitor of MAO-B, a serotonin antagonist and CNS stimulant. Long-term smokers usually have only 40-60% of normal MAO-B activity.

== Water maze vs. Conventional mazes ==

Combined use of non-selective MAO inhibitors or MAO-A inhibitors and serotonergic drugs is likely to lead to [[serotonin syndrome]].

Watermaze has advantages over conventional mazes (e.g., [[plus maze]]). There are no [[local cue]]s such as [[scent trace]]s; no fixed escape-fomula; the rat makes good progress in the trials because it wants to escape. Rats are natural swimmers – they are not distressed but they do want to find that platform. Mice have an option to float, and maybe this is why they are not so cooperative in watermaze. It has been suggested that they don’t aim to find the platform, but trick the technician into rescuing them.

MAOIs, often in the form of harmal, are also sometimes used with [[hallucinogenic drug]]s, many of which are potentiated. [[Ayahuasca]] (''[[Banisteriopsis caapi]]'', containing harmala, combined with a [[Dimethyltryptamine|DMT]] admixture such as ''[[Psychotria viridis]]'') is the most common such combination. The effects of LSD appear to be diminished or abolished by MAO-A inhibition.

== Watermaze analysis ==

Monoamine oxidase inhibitors include:

The earliest and classic measure of learning is ''[[Latency (engineering)|latency]]'', which refers to the amount of time it takes to find the platform. However, rats can cheat. They might guess an area and swim a search pattern, getting to the platform quite quickly. There is a whole bunch of further analyses, which can tease out true spatial learning. The same swim is used, but a [[video tracker]] is required. Professional systems come with a suite of analysis features to extract measures such as time and path in [[quadrant]]s, near platform, in any specified area. The [[Gallagher measure]] looks for average distance to platform. The [[Whishaw corridor test]] measures time and path in a strip from swim-start to platform.

* [[Isocarboxazid]] (Marplan)

Mice are smart

* [[Moclobemide]] (Aurorix, Manerix, Moclodura®)

* [[Phenelzine]] (Nardil)

* [[Tranylcypromine]] (Parnate)

* [[Levo-deprenyl]] (Selegiline, Eldepryl)

* [[Harmala]] (present in [[Harmal]], ''[[Banisteriopsis caapi]]'', and [[tobacco]]; also acts as a serotonin antagonist and CNS stimulant).

== Atlantis platform ==

[[Category:Antidepressants]]

[[Category:Monoamine oxidase inhibitors|*]]

A more advanced way to stop the rats cheating is the [[Atlantis rising platform]], which stays deep in the water and only rises when the rat lingers at the right place.

[[de:Monoaminooxidase-Hemmer]]

[[fr:IMAO]]

== References ==

[[he:מונואמין אוקסידאז]]

[[pl:Inhibitory monoaminooksydazy]]

* Davis S, Butcher SP, Morris RG. "The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro." ''J Neurosci''. 1992 Jan;12(1):21-34. PMID 1345945

[[pt:Antidepressor inibidor da MAO]]

* Liang KC, Hon W, Tyan YM, Liao WL. "Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze." ''Chin J Physiol.'' 1994;37(4):201-12. PMID 7796636

[[de:Morris-Wasserlabyrinth]]

==External links==

* [http://www.hvsimage.com/papers/index.htm Watermaze publications 1966-2002]

* [http://neco.mitpress.org/cgi/content/abstract/10/1/73 Information on the hippocampus]

* [http://www.mailtalk.ac.uk/archives/watermaze.html The UK Academic Watermaze Discussion Group]

[[Category:AntidepressantsMazes]]

[[Category:Neuroscience]]