6-OHDA & DSP-4

Stephan Anagnostaras stephan at psych.ucla.edu
Wed Apr 19 01:02:05 EST 1995

In article <798225072snz at longley.demon.co.uk>, David at longley.demon.co.uk wrote:

> Is anyone out there still doing any work with these neurotoxins with an aim
> to understanding the role which CNS monoamines play in behaviour? Are there
> any new catecholamine neurotoxins? Has anyone come up with a selective 
> Dopaminergic neurotoxin (like DSP-4 is for NA of Locaus Coeruleus origin)?

Sure I have done lots of this kind of stuff.

There are a few CA neurotoxins.  The most useful experimentally has
been 6-OHDA.  Since 6-OHDA kills both DA and NE cells, you can
prevent damage to the one you dont want to kill by injecting the 6-OHDA
only into regions where you know only one kind of cell exists (NE or
DA).  Alternatively, you can block the reuptake transporter for
either DA or NE (preventing damage to that type of cell since 6-OHDA
is taken up thru this transporter).  This is easy for NE, you can
use desipramine (25-40 mg/kg ip) and restrict your damage to just
DA.  This is more difficult for protecting DA, since most reuptake
transporters for DA also block NE.  However, there is one highly
selective DA reuptake blocker, GBR-12909, which is available commercially
(RBI) and has been used in vitro.  Either procedure will entirely
protect the system you don't want to damage and annihilate the one you
want to if you carefully select the doses.  DSP4 for NE has also been
used extensively, but the procedure is not as sophisticated as the
6OHDA procedure is for DA, and the damage is more specific than you
have described.  

There are other CA neurotoxins, e.g., MPTP, but most of these are very
expensive and dangerous to work with (i.e., why do you need a different
CA toxin??).

Anyway, you can probably ask all of these questions better using other
less permanent techniques.  Safe and tested receptor antagonists for
all the monoamines exist so these are probably a better choice than
neurotoxic lesions if you want to ask about how they regulate behavior
(rather than how a structure is involved; then the lesion would be
more appropriate). You can aslo try drugs which block synthesis,
which are also like reversible type lesions (e.g., AMPT for
blocking DA and NE synthesis).

Good luck


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