Place cells and addictive drugs

David Longley David at longley.demon.co.uk
Thu Jun 17 14:20:00 EST 2004

In article <6e2f1d09.0406170830.1ca99238 at posting.google.com>, Glen M. 
Sizemore <gmsizemore2 at yahoo.com> writes
>> B: My idea basically stemed from the fact that people always look at
>> synaptic placsticity in the VTA or the Nucleus Accumbens when they are
>> interested in drugs of abuse..
>> GS: Do they look for "plasticity?" People, no doubt look at the NAcc
>> after exposure to self-administered drugs (or drugs administered
>> response-independently), but you almost seem to be implying that it is
>> this site where "learning takes place." I think that the role of the
>> NAcc is thought to be more of the place where "reinforcement signals"
>> are generated. Certainly, though, changes in the NAcc after extended
>> exposure to the drug might be thought to reflect the change from
>> "recreational use" to "addiction."
>B: No, they really do. Looks at TIPS, vol 26 No 4. I quote "Other
>studies have focused on influences by drugs of abuse on synaptic
>and/or plasticity in the VTA".
>GS: But I think that a lot of these studies are looking at changes in
>the VTA, NAcc, VP etc. as a function of extended exposure to drugs.
>No? I don't think the notion ever was "this is where the learning
>takes place." Indeed, I'm not sure most people regard "addiction" as
>primarily a learning phenomenon. Certainly, learning to
>self-administer a drug puts one on the road, and it is clear that
>(most) drugs of abuse (DOA) function as reinforcers in non-humans, but
>the notion is that the whole motivational system goes out of whack as
>a function of repeated self-administration (and the neurochemistry is
>different when the drug is self-administered – at least with cocaine).
>> B:  I don't really know why, I wouldn't have
>> thought palsticity there would have explained addiction very well. I
>> always thought that plasticity in the cortex would have far more
>> interesting, i.e. when the reward coincides with a stimuli, then the
>> cortical cells which code/interpret/are activated by that stimuli will
>> strengthen there synapses with other downstream neurons, increases the
>> attentional weighting of the stimuli. But it would be very hard to
>> find a
>> neuron which is strongly activated by a particular stimuli (I assume).
>> So
>> I thought, place cells seem easy enough to find...
>> GS: Perhaps the NAcc, and other parts of the basal ganglia and VTA
>> etc., produce a diffuse release of neurotransmitter into the PFC,
>> association cortices etc., and this produces LTP in the synapses
>> between sensory related neurons and motor related neurons. Here, the
>> "plasticity" could be "in the cortex," in the sense that that it is
>> here that a crucial step is occurring, and changes in NAcc function
>> (another kind of plasticity) would drive the "cortex system." I'm not
>> really advocating this, I'm just pointing out the ambiguity of your
>> question.
>B: Well thats exactly how I would have expected people would have
>thought it
>would happen, an increase in cortical synaptic strength.
>GS: Again, that is how the self-administration responses are acquired,
>but "addiction" is thought not to be "mere" self-administration, and
>the changes that take a person (or animal) from "recreational use" to
>"addiction" may have nothing to do with the changes that occur when
>the animal first learns to self-administer the drug. But I don't take
>any firm stances here; my opinion is that we are so far away from
>understanding something as "simple" as what goes on when an animal
>acquires some operant response that it is laughable. Even if the NAcc
>did what some have claimed (i.e., mediate all reinforcement), we still
>would not be close to understanding how non-reflexive, spontaneous
>responses come to be more probable because of their consequences.
>> GS: Fortunately or unfortunately, if you can drive a 20-electrode
>> gizmo into a rat's head and find orderly relations between behavior
>> and physiology, you can pretty much make up any silly story you want
>> to, and it'll be called "science."
>B: But of course, I've realised the flaw in my proposed experiment,
>hippocampal place cells (at least in theory) represent current
>not the goal. What I would want to do, is record from prefrontal
>(or perhaps supplementary motor cortex) cells which represent goals.
>read a couple papers about them (goal cells), one done in humans,
>the old taxi driver game, but there doesn't seem to be such a reliable
>way of recording them. Still... it was a nice idea
>GS: Hmmm…….yes, I suppose that recording from cells while an animal is
>behaving is worthwhile, but the problems with much of behavioral
>neuroscience,  IMO, is largely its conceptual structure. My guess is
>that "goal cells" will eventually be seen as a silly notion, as will
>representation (but not "mapping") and a host of other things borrowed
>from our folk-psychology vernacular. No offense intended.
>BilZ0r <BilZ0r at TAKETHISOUThotmail.com> wrote in message 
>news:<Xns950B89FE5BAE1BilZ0rhotmailcom at>...
>> gmsizemore2 at yahoo.com (Glen M. Sizemore) wrote in

Not that you'll be surprised to hear it, but I agree. If they are not 
doing so already, I think there are many reasons why people should 
*radically* question the way that people talk about the monoamines and 
"reinforcement" and especially "reinforcement centres" (and for what 
it's worth, I've covered those in some detail both here and elsewhere 
over recent years - albeit with few comments being made). When I began 
work in this area nearly 25 years ago these sorts of ideas were already 
pretty well entrenched and one of the first papers I was given by my 
thesis supervisors before I started was one they'd published together in 
Research Advances in Alcohol and Drug Problems Vol 4, eds Y Israel, F B 
Glaser, H Kalant, R E Popham, W Schmidt & R J Smart, Plenum Pubs. 1978 - 
T. J Crow & J F W Deakin "Brain Reinforcement Centers and Psychoactive 

The enormous investment in the pharmacology, neurochemistry and 
neuroanatomy of the monoamine systems over the past fifty years may have 
led to some well deserved prizes, but I personally think much, if not 
most of the mammalian behavioural work is just very poor science.

If anyone would like to challenge that with some good examples, I'd be 
very interested (and very grateful) to hear it.

David Longley

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