Thursday, April 06, 2006

Quick Post That Will Make Sense to Maybe One Person Who Reads This (Or More)

So I've been working on this paper all week, and I was telling everyone the last couple of days that it all made sense so long as psychostimulant sensitization-induced LTD was mediated by a change in AMPAR function rather than endocytosis.

I realized this afternoon that I was wrong, due to something key that I'd forgotten about the Marina Wolf paper I'd been reading on Monday, which I shan't go into right now.

But anyways, I realize that this afternoon and what's the next paper I grab from the pile of stuff I need to read? This:
Nucleus accumbens long-term depression and the expression of behavioral sensitization

The abstract:

Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs of abuse. Molecular mechanisms that are critical for behavioral sensitization have yet to be specified. Long-term depression (LTD) of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)-mediated synaptic transmission in the brain has been proposed as a cellular substrate for learning and memory. The expression of LTD in the nucleus accumbens (NAc) required clathrin-dependent endocytosis of postsynaptic AMPARs. NAc LTD was blocked by a dynamin-derived peptide that inhibited clathrin-mediated endocytosis or by a GluR2-derived peptide that blocked regulated AMPAR endocytosis. Systemic or intra-NAc infusion of the membrane-permeable GluR2 peptide prevented the expression of amphetamine-induced behavioral sensitization in the rat.
(emphasis mine)

I'm glad I figured that out this afternoon, because otherwise I'd spend this entire paper trying to figure out how they got it wrong. ;-P

8 Comments:

At 07 April, 2006 01:21, Anonymous Anonymous said...

thought i might be that one person but noo.. never understood the fuzz about sensitization to narcotics, it doesn't strike me as an important aspect of human drug addiction. what am i missing?

cool blog btw

/chris (blogs.warwick.ac.uk/christopherharris)

 
At 07 April, 2006 02:37, Blogger The Neurophile said...

The short version is that sensitization is important mainly because
A: it's an easy model
B: it's not strictly learning-dependent.

There are ways you can make interventions that it's not necessarilly clear in models like CPP or self-administration whether you're affecting the actual response to the drug or whether you're affecting other secondary aspects--like learning--that can be difficult to tease apart even with controls.

Sensitization, on the other hand, seems to be a more direct correlation to the alterations in incentive salience being caused by the drug. And, again, it's by far the easiest to perform and has the least fear that a slight change in your protocol could lead to a large difference in results. At least, imho.

 
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