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THC Neuropharmacology

THC affects Short Term Learning by binding to areas in the Hippocampus (Memory Consolidator), Basal Ganglia(Movement/Reward), and various cortical areas. There seems to be little doubt most cannabis users experience some sort of learning problems while they are high, however, from personal experience I would say the short term effects are not permanent, as I have carried a 4.0 throughout high school and 2 yrs of uni, smoking 1-6 times a day along with other drugs. Your mind is so powerful and full of potential you can overcome almost anything with willpower and inner strength. (see transcendental meditation) But you don't need to be a guru to figure out the anxiety you experience might be just as real as your vision of the computer screen. Yet you can shut off the anxiety, just as you shut off your vision when you shut your eyes. Things/Ideas/Reality are just as real as you make them. You don't learn in school because you don't have the motivation, or maybe you do, but you use pot to rationalize not learning. Trying smoking and exercising, you learn a lot about yourself running around getting lost and thinking. Try smoking pot and swimming, reading, chess, hiking, etc...You don't have to be in a starched classroom trying to memorize boring and unapplicable facts. The point is that THC will produce only the obstacles you create for yourself. <Cue Marley> Hey doyahavinthingonya?
 
Slaughterhousefive42 said:
What is your reasoning to support your assumption that anxiety isn't dopamine related? In fact, dopamine is released in response to ANY salient stimulus, either rewarding or negative. This DA release is found in various parts of the brain, especially the Prefrontal cortex and the striatum. As anxiety is a construct made up by psychologists, it is incorrect to associate one neurotransmitter (noradrenalin) with so-called anxiety. Anxiety is the result of a complex interaction of various NT, 2nd messenger, effector, transcription factors, and who knows what else, glial cells, etc...Noradrenaline might be a player in the cascade of neural events producing the construct defined as anxiety, but it is surely not sufficient, and probably not even necessary in all cases.
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I believe in the schema of anxiety and panic layed out by McNaught and Gray, which can be seen here

The Neuropsychology of Anxiety: An Enquiry into the Function of the Septo-hippocampal System, 1982; The Neuropsychology of Anxiety, 2000

here

McNaughton N, Gray JA.
Anxiolytic action on the behavioural inhibition system implies multiple types of arousal contribute to anxiety.
J Affect Disord. 2000 Dec;61(3):161-76

and most recently

McNaughton N, Corr PJ.
A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance.
Neurosci Biobehav Rev. 2004 May;28(3):285-305

It moves away from the basically retarded DSM views of anxiety and panic as some kind of wishy washy terms for things when people kinda freak out sorta... I mean, they don't even really define them as seperate things. It forms a behavioural and pharmacological hierarchy. To quote:

"It is based on two behavioural dimensions: 'defensive distance' as defined by the Blanchards and 'defensive direction'. Defensive direction is a categorical dimension with avoidance of threat corresponding to fear and approach to threat corresponding to anxiety. These two psychological dimensions are mapped to underlying neural dimensions. Defensive distance is mapped to neural level, with the shortest defensive distances involving the lowest neural level (periaqueductal grey) and the largest defensive distances the highest neural level (prefrontal cortex). Defensive direction is mapped to separate parallel streams that run across these levels. A significant departure from prior models is the proposal that both fear and anxiety are represented at all levels"

The idea being that when the defensive direction is to approach a possible threat, you get anxiety, and when the direction is to avoid, you get panic.

I mean, of course noradrenaline is one the most important players in anxiety, peripheral NA can induce panic attacks and anxiety by itself. Central or peripheral blockade of adrenoreceptors can block anxiety extremely well. When was the last time someone got prescribed a dopamine antagonists for their anxiety?
 
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Strange how people think that other people who smoke weed are stupid, when they aren't at all...some people in these threads are so smart when it comes to this it scares me...I think that some people who smoke do it because they think to much :)
 
If weed makes you feel stupid you need to find some higher quality weed. With some good bud your analytical mind goes into overdrive.
 
Slaughterhousefive42 said:
In fact, dopamine is released in response to ANY salient stimulus, either rewarding or negative.
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This is pretty controversial, as there is lots of conflicting evidence. A lot of people are trying really hard to prove that DA is only released in response to appetitive stimuli, but its still a matter of intense debate.

As for the whole anxiety debate you guys are getting into, it seems to me that BilZ0r has bought into this guy McNaughtons theory pretty heavily. That is not to say that NE doesnt play a major role, but you cant reduce the etiology of anxiety down to just one neurotransmitter. Serotonin also seems to be very important as well; many anxiety drugs on the market seem to exert their effects at least in part through serotonergic signaling.
 
I missed that quote, yeah, that is a big one. I would say that dopamine gets released in response to novel, or 'emotively weighted' stimuli or something like that. I'm have the ole' dopamine debate in a thread in DB called "Heroin and Nicotine"

You should read the paper in Neurosci Biobehav Rev man, it's actaully preety good. Now I may have been swayed by the fact that McNaughton lectured me in a biopsychology paper, but still... lol

Meanwhile, I definatly think 5-HT has a role man, don't get me wrong, just NA also had a major role.
 
What good are scientific views if you can't back them up with others hard-earned experiments?
Well, here's some contemporary research that supports my belief that dopamine is released in response to any salient stimulus, especially in the striatum and the prefrontal cortex:
"Human striatal response to salient nonrewarding stimuli."
J Neurosci. 2003 Sep 3;23(22):8092-7
PubMed: 12954871

"Stimulus-specific plasticity of prefrontal cortex dopamine neurotransmission."
J Neurochem. 2004 Mar;88(6):1327-34
PMID: 15009632 (pubmed.com)

"How antipsychotics become anti-'psychotic' - from dopamine to salience to psychosis."
Trends Pharmacol Sci. 2004 Aug;25(8):402-6.
PMID: 15276708

Coming from Dr. John Bruno of OSU, in his grad school class last qtr he stressed dopamine was released in response to ANY salient stimulus, not just rewarding ones as previously thought.

I agree with 5-HT2 that you cannot reduce the etiology down to just one neurotransmitter. NE might be sufficient to cause anxiety, but I would hesitate to assume it is necessary.
 
I think pot increases serotonin and dopamine (and extra dopamine triggers NA release) and when it wears off all these neurotransmitters are somewhat depleted. I don't feel like mentioning sources and my reasons now but this is what I believe.
 
Well I suppose it depends on how we're going to define this doesn't it. When I'm talking about dopamine release, normally I'm not talking about striatal stuff, because thats all movementy, and I don't really know what the fuck is going on there (not that that discounts it, just that that's not what Im talking about).

When it comes to basal forebrain dopamine release, and hence microdialysis, I'm talking about a statistically significant increase in dopamine in the perfusate, from an awake animal in some kind of null condition... i.e. in a box, with no food no noise and no outside activity. Now of course, there is a basal dopamine release, but you get a basal release when the animal is anaethetised so that can't be in responce to salient stimuli.

I wonder if the dopamine release in an awake animal is that much different from the release in an anaethetised animal?

Meanwhile, I'd like to see you show that a gentle noise played to a rat increase recordable dopamine outflow.

None of your citations showed that all salient stimuli cause dopamine outlfow BTW. That first one is quite interesting, but I would say that the fact that the subjects had to respond drastically changes the nature of the experiment. Because now you're not just inducing concentration/salience, you making the subjects respond, which could make the experiment some kind of coditioning experiment. You could also argue that sucessfully completing the response would be some kind of interoceptive reward.

You sure your Dr Bruno wasn't stressing that dopamine release happens not only to rewards, but to "emotively salient" stimuli?
 
Well, these neurophysiological studies are definitely talking about increases in phasic rather than tonic activity, which could also account for the elevated dopamine concentrations measured by microdialysis. Need to look at more refs, but I have to go home now.

Mirenowicz J, Schultz W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature. 1996 Feb 1;379(6564):449-51.

Waelti P, Dickinson A, Schultz W. Dopamine responses comply with basic assumptions of formal learning theory. Nature. 2001 Jul 5;412(6842):43-8.

Ungless MA, Magill PJ, Bolam JP. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science. 2004 Mar 26;303(5666):2040-2.
 
I have been taught dopamine more often than not operates in phasic/almost hormonal fashion.

Dr. Bruno quite possibly could have been stressing that Bilz0r, I will clarify with him. How do you define "emotively salient" in a rat by the way?

If rats are trained to attend and disattend to stimuli, there is activity in the VTA-->NAC-->BFCS->>cortex network(highly simplified), which involves dopaminergic release from the VTA efferent converging with hippocampal, amygdala, and cortical inputs in the Nucleus Accumbens Shell.

So the microdialysis studies at the Bruno/Sarter lab would point toward at least some dopamine release in response to significant stimuli, whether it be "emotive" or non-emotive.
 
Slaughterhousefive42 said:
If rats are trained to attend and disattend to stimuli, there is activity in the VTA-->NAC-->BFCS->>cortex network(highly simplified), which involves dopaminergic release from the VTA efferent converging with hippocampal, amygdala, and cortical inputs in the Nucleus Accumbens Shell.

So the microdialysis studies at the Bruno/Sarter lab would point toward at least some dopamine release in response to significant stimuli, whether it be "emotive" or non-emotive.
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Yes, but is that dopamine release correlated with spiking activity in the VTA, or is it instead independent of impulse flow (i.e., not phasic in the traditional sense of the term) and mediated by local signaling of some sort? The neurophysiological data suggest that only appetitive stimuli cause burst firing.

Also, if the probability of reward is around 0.5 (Id have to look at the methods in the microdialysis studies to see if this applies), then there will be an increase in DA neuron firing in response to a stimulus that may be associated with it, as described in:

Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science. 2003 Mar 21;299(5614):1898-902.
 
So the microdialysis studies at the Bruno/Sarter lab would point toward at least some dopamine release in response to significant stimuli, whether it be "emotive" or non-emotive
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That is basically what I'm talking about. Significant in that an animal should learn what stimuli preceded it. As I say, a gentle clicking noise is salient to a rat (at least in my opinion), but wont cause dopamine release. Pair the clicking noise with food, and after a couple repititions, the noise will now cause dopamine release.

Meanwhile, I agree, the idea of action-potential dependent flow is interesting. Because of the monkey electrophysiological data that shows that only rewards activate VTA neurons. Yet there could be presynaptic influences that cause release otherwise.

Also, I'm wondering about the topogrpahy of the NAc... not just shell vs core, but other stuff to. Does anyone know anything about that in regards to say, yoked cocaine administration, or negative vs positive rewards, or important stimuli?
 
Dr. Bruno reiterated to me today that a gentle noise will cause at least some dopamine release, because of dopamine's involvement in regulating the Basal Forebrain Cholinergic System necessary for attentional processing. So basically if a rat is paying attention to a stimulus, Bruno's research would say dopamine is being released, if not by the VTA but by the top-down PFC regulators in the NAC.

There's dopamine being "released" every millisecond in our brain by some presynaptic or AP dependent mechanism, not to mention glial cells, so it would be hard to prove significant/emotive stimuli are necessary for dopamine release, and not just simple novel stimuli such as the clicking noise BilzOr mentioned.

In our microdialysis studies we infuse multiple pharm. challenges into the NAc shell, including amphetamine/cocaine, ritalin, CPP (Glu Antagonist), NMDA (Glu Agonist), as well as other dopamine agonist/antagonists. The shell seems to be the site of convergence of multiple NAC inputs, therefore influencing the NAC's GABAergic control over the BF and thus the pFC.
 
Slaughterhousefive42 said:
There's dopamine being "released" every millisecond in our brain by some presynaptic or AP dependent mechanism, not to mention glial cells, so it would be hard to prove significant/emotive stimuli are necessary for dopamine release, and not just simple novel stimuli such as the clicking noise BilzOr mentioned.
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That was sorta my point. That of course there is going to be a "release" of dopamine which is coincidental with any stimulus (whether it is causual or not), I just don't know how you'd proove causality.

If your lab is dopamine/acetylcholine, you might be familar with the work of Brian Hyland, From articles like:

Reynolds JN, Hyland BI, Wickens JR.
A cellular mechanism of reward-related learning.
Nature. 2001 Sep 6;413(6851):67-70

I spent some time in his lab when I was in 2nd year.
 
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