LSD and dopamine (nichols paper)

[vecktor]

from Nichols:
http://www.unboundmedicine.com/medl...erent_than_the_first_temporal_phase_of_action
possibly the unique profile of LSD has something to do with the delayed action dopaminergic effects. LSD 90 in the abstract refers to the action of LSD at 90 minutes rather than any new flavor of LSD.

Pharmacol Biochem Behav 2007 Jun 14.
Abstract Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time (LSD-30, N=12) or a 90 min preinjection time (LSD-90, N=13) from saline, using a two-lever, food-reinforced operant conditioning task. We then tested a large number of agonists and antagonists belonging to distinct pharmacological classes in these animals. As anticipated, classical hallucinogens such as psilocin and mescaline substituted only in LSD-30 rats, and not in LSD-90 rats. The dopamine receptor agonists ABT-724, aripiprazole, dihydrexidine, WAY 100635, and SKF 38393, fully or partially mimicked LSD-90, but not LSD-30. The results reported here support and extend our previous conclusion that the delayed temporal effects of LSD are mediated by activation of a dopaminergic system.

 

[egor]

^^interesting theory, I wonder if any other ergolines work on dopamine the same way, or if this is unique to lsd

 

[5-HT2]

This may be why LSD keeps you up and wired for so long on the comedown

 

[LuxEtVeritas]

it notes some of the DAR agonists FULLY mimicked LSD90....?

Huh...?

 

[DadeMurphy]

In this specific rat model...
which doesn't necessarily suggest that the DAR agonists are in any way psychedelic in people.

 

[vecktor]

^ it also shows the limits of using rat models, as you never know which cue they are discriminating for.
I am thinking of the MDAI MMAI MDMA substitution in particular.
V

 

[5-HT2]

^^^alternatively, it could be due to a pharmacokinetic difference between rodents and humans: i.e., the psychedelic effects of LSD had ceased 90 minutes after injection.

 

[vecktor]

^^^alternatively, it could be due to a pharmacokinetic difference between rodents and humans: i.e., the psychedelic effects of LSD had ceased 90 minutes after injection.

good point, that hadn't occurred to me.

 

[fastandbulbous]

I've long thought that it was the dopaminergic side of LSD that made it so 'in your face'. For mme, most psychedelics wax & wane in their effect during the peak, but LSD is relentless in it's psychedelia

I found that other psychedelics (mainly psilocybin) when combined with amphetamine produced that same relentlentless push during the peak

 

[nuke]

I've long thought that it was the dopaminergic side of LSD that made it so 'in your face'. For mme, most psychedelics wax & wane in their effect during the peak, but LSD is relentless in it's psychedelia

I found that other psychedelics (mainly psilocybin) when combined with amphetamine produced that same relentlentless push during the peak

Yeah, I always thought that a low dose of LSD reminded me of speed, I'd always be up all night dancing and moving around.

 

[5-HT2]

The only question is whether the receptor binding data for LSD and DA agonists are consistent with the behavioral data. If somebody has the motivation to do the extensive collation and comparison of PDSP data that this analysis requires, that'd be great. Perhaps I'll give it a shot when I get home internets.