Posted by pseudoname on November 25, 2005, at 19:50:25
In reply to Re: caffeine reading » pseudoname, posted by lunesta on November 24, 2005, at 13:26:41
Hey, lunny.
> ...unless you can cite more evidence, i dont think caffeines antidepressant activity is via dopamine?
I thought you might find these references interesting, particularly the ones about the adenosine connection. Not all of the papers are available online, but you probably have school access to them.
I began by looking at Hughes et al (Caffeine and Schizophrenia. <Psychiatric Services> 1998; 49:1415-1417 http://ps.psychiatryonline.org/cgi/content/full/49/11/1415), who summarized the research this way: "Caffeine has well-documented effects on dopamine...."
Kaasinen et al (Dopaminergic effects of caffeine in the human striatum and thalamus. <Neuroreport> 2004; 15(2):281-285 http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200402090-00014.htm) summarized their own research this way: "The findings indicate that caffeine has effects on dopaminergic neurotransmission in the human brain, which may be differential in the striatum and the thalamus."
You found Nehlig (Are we dependent upon coffee and caffeine? A review. <Neuroscience & Biobehavioral Reviews> 1999; 23(4): 563-76 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=99171902&dopt=Citation) unpersuasive by herself, but the article *is* scholarly and supports the nontrivial involvement of dopamine: "[C]affeine doses that reflect the daily human consumption, do not induce a release of dopamine in the shell of the nucleus accumbens but lead to a release of dopamine in the prefrontal cortex, which is consistent with caffeine{'s] reinforcing properties." Incidentally, Nehlig wrote the book on "Coffee Tea Chocolate and the Brain."
Mumford & Holtzman (Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. <Journal of Pharmacology and Experimental Therapeutics> 1991; 258:857-865 http://jpet.aspetjournals.org/cgi/content/abstract/258/3/857) trained rats to recognize when an injection was a relatively low dose of caffeine rather than saline. When the rats were then injected with drugs known to activate dopamine receptors, they responded as though getting caffeine.
"The positive stimulatory effects of caffeine appear in large measure to be due to blockade of [adenosine] A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum." –Daly & Fredholm (Caffeine: an atypical drug of dependence. <Drug and Alcohol Dependence> 1998; 51:199-206 http://www.anakata.hack.se/papers/pdf/Drug_Alcohol_Depend-51-199.pdf)
"Activation [by caffeine] of the [adenosine] A2a receptor makes dopamine less efficient as a neurotransmitter; thus, by blocking this receptor, caffeine enhances the ability of dopamine to function as a neurotransmitter" –Hughes et al. citing Ferre et al (Adenosine-dopamine interactions in the brain. <Neuroscience> 1992; 51:501-512 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1488111&dopt=Abstract )
Garrett & Griffiths (The role of dopamine in the behavioral effects of caffeine in animals and humans. <Pharmacology, Biochemistry and Behavior> 1997; 53:533-541 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9218278&dopt=Citation) summarize their study this way: "Thus, caffeine, as a competitive antagonist at adenosine receptors, may produce its behavioral effects by removing the negative modulatory effects of adenosine from dopamine receptors, thus stimulating dopaminergic activity. ... Furthermore, caffeine potentiates the effects of dopamine-mediated drugs on these same behaviors, and some of caffeine's effects on these behaviors can be blocked by dopamine receptor antagonists."
"Caffeine appears capable of *priming* the dopaminergic reward circuitry that is important to cocaine-abuse" [emphasis added]. –Horger et al (Caffeine exposure sensitizes rats to the reinforcing effects of cocaine. <Neuroreport> 1991; 2:53-56 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1768850&dopt=Abstract)
Remember, the assertion I am disputing is that caffeine "doesnt work via dopamine @ all." As I said in my original response,
> And the fact that caffeine blocks adenosine doesn't mean that caffeine doesn't also "work via" DA.
Anyone, like spriggy in the original post, who notices a consistent antidepressant response from caffeine should not be discouraged from inquiring about dopamine. The level of detail implied by these questions...
> What receptors does [caffeine] effect exactly, auto receptors, post synaptic? is it in an area that matters?
...perhaps can't be satisfied at present. But that doesn't make the caffeine-dopamine connection any more dubious than many accepted psychiatric drug mechanisms. Far from it. And what area of the brain doesn't "matter" for these issues? How would we know?
> The evidence you cite doesnt personally convince me of dopamine involvement in the rewarding and antidepressant effect of caffeeine
That may still be true. But the fact that virtually every scientific article on the human physiology of caffeine begins with some version of "The mechanisms remain elusive..." says to me that no one should simply tell depressed caffeine-responders seeking information that there is no such connection. To me, that seems heedless.
Thanks for dialoguing, lunny. I for sure learned something.
poster:pseudoname
thread:580785
URL: http://www.dr-bob.org/babble/20051119/msgs/582207.html