leungkachong
Bluelighter
Hammy mentions the idea of DA signalling as 'driving' not 'pleasure-inducing'; I think understanding the bleeding edge of neuroscience related to this is likely relevant to all BL ADD'ers (hence the end of my multiyear hiatus to post this). What he was referring to was the neuropsychopharmacological model for the mesolimbic DA projection path (VTA-to-N.Acc) often referredto as 'incentive salience'/'incentive sensitization'. This is borne out of it being possible to have dissociation (the experimental outcome kind, not the k-tarded kind) between euphoria/reward and ectopic recruitment of incentivization... and that we only really have experimentally support/verification for the latter (not to mention that any junkie could figure this shit out if they sat and thought about it long enough)
You start to get the jist of the concept when you look at pathophysiologies of the DA projection pathway. I'm going to use the examples of Tourettes and OCD, which are redonkulously comorbid.
-The first involves fairly involuntary, simple motor actions that can be partially inhibited by the individual and includes a feeling of urgent need prior to tic'ing.
-The other involves unmanagable preoccupation (obs.) which necessitates the need to perform certain tasks/actions (comp.).
-The most efficacious pharmacological agents for both conditions are the old DA antagonists (non-atypical neuroleptics). Not to mention that both conditions associate strongly/best with ventral striatum in fMRI. Oh and not to mention that the looking at DAT/AAAD activity using ligand assisted imaging techniques points back to striatum.
---This makes locomotor-sense for both conditions, via our nigrostriatal DA-projections driving the stereotypy. And, after noting that the the ventral striatum is home to the Nucleus Accumbens, aka- the post-synaptic target of the ventral tegmental projections for the *cough* mesolimbic pleasure-path')... this explains the occurance of the urge and preoccupation as "mis-incentivization" disorders.
-But then you gotta ask, why the fuck isn't there mesolimbic-mediated euphoriant effects in these two conditions?
Importantly to note from this, is that the self-administration methodologies for an agonist cannot distinguish if a drug is reward/pleasure inducing, just that it is reinforcing via the 'mesolimbic incentivo-genic (nb: not a real word) pathway'.... it would be kinda like pharmacologically-inducible OCD). It also provides an answer to the age-old conundrum of why isn't DA agonism sweet-ass, and why would increasing tonic neurotransmission with an agonist cause instead individuals to seek those things that have high attribution of incentive already (gambling, freaky-deaky paraphilias, etc).
ps - I guess maybe if your bulimic, DA agonists might induce reward/hedonia via binding in the area postrema, hahhahah.....
You start to get the jist of the concept when you look at pathophysiologies of the DA projection pathway. I'm going to use the examples of Tourettes and OCD, which are redonkulously comorbid.
-The first involves fairly involuntary, simple motor actions that can be partially inhibited by the individual and includes a feeling of urgent need prior to tic'ing.
-The other involves unmanagable preoccupation (obs.) which necessitates the need to perform certain tasks/actions (comp.).
-The most efficacious pharmacological agents for both conditions are the old DA antagonists (non-atypical neuroleptics). Not to mention that both conditions associate strongly/best with ventral striatum in fMRI. Oh and not to mention that the looking at DAT/AAAD activity using ligand assisted imaging techniques points back to striatum.
---This makes locomotor-sense for both conditions, via our nigrostriatal DA-projections driving the stereotypy. And, after noting that the the ventral striatum is home to the Nucleus Accumbens, aka- the post-synaptic target of the ventral tegmental projections for the *cough* mesolimbic pleasure-path')... this explains the occurance of the urge and preoccupation as "mis-incentivization" disorders.
-But then you gotta ask, why the fuck isn't there mesolimbic-mediated euphoriant effects in these two conditions?
Importantly to note from this, is that the self-administration methodologies for an agonist cannot distinguish if a drug is reward/pleasure inducing, just that it is reinforcing via the 'mesolimbic incentivo-genic (nb: not a real word) pathway'.... it would be kinda like pharmacologically-inducible OCD). It also provides an answer to the age-old conundrum of why isn't DA agonism sweet-ass, and why would increasing tonic neurotransmission with an agonist cause instead individuals to seek those things that have high attribution of incentive already (gambling, freaky-deaky paraphilias, etc).
ps - I guess maybe if your bulimic, DA agonists might induce reward/hedonia via binding in the area postrema, hahhahah.....
