Posted by Shawn. T. on July 29, 2002, at 1:53:25
In reply to Victimization, posted by EmilyAnn on July 26, 2002, at 13:47:57
I understand exactly how you feel. There is absolutely no reason why you should feel guilty. It is, emphatically, not your fault. I believe that a lot of attitudes need to change in the world. I believe that the following is concrete scientific proof supporting these claims. Note that 5-HT stands for serotonin, and 1b is one among several types of serotonin receptors.
"The results support the hypothesis that 5-HT(1B) receptors within the VTA can function as heteroreceptors to inhibit GABA release(1)."
"5-HT-moduline, an endogenous tetrapeptide, regulates the efficacy of these 5-HT1B receptors, hence, is able to control the serotonergic activity in a synchronous manner for the various varicosities from a single neuron and thus may favour the differential effect of that neuron on distinct cerebral functions. Accordingly, the peptide allows the 'fine tuning' of the cerebral activity by the serotonergic system to elaborate the response given by the brain to a particular stimulus, that is, stress situations."
5-HT-moduline acts as an antagonist at 5-HT1b receptors. A logical conclusion would be that 5-HT-moduline causes the release of GABA (an inhibitory neurotransmitter) in the ventral tegmental area (VTA) of the brain.
"Overall, the results of this study suggest that terminal DA release in the ACB is under tonic GABA inhibition mediated by GABAA (and possibly GABAB) receptors, and tonic cholinergic excitation mediated by both muscarinic and nicotinic receptors. Activation of GABAA (and possibly GABAB) receptors within the ACB may be involved in the feedback inhibition of VTA DA neurons.(3)"
So 5-HT-moduline, via 5-HT1b antagonism, causes the release of GABA in the VTA. This results in an increase of the GABAergic inhibition of terminal dopamine (DA) release in the nucleus accumbens (ACB). Likewise, dopamine release in the ventral tegmental area is diminished by 5-HT-moduline (4). The VTA - nucleus accumbens pathway undoubtedly plays a major role in the brain's reward mechanisms (5).
"... Local application of 5-HT1B antagonists decreased the rate of clearance of the serotonin signal comparably to the selective 5-HT uptake inhibitor (SSRI), fluvoxamine. (6)"
For the first few weeks of SSRI treatment, a very common side effect is increased anxiety. I contend that these drugs exert their effects by essentially "dulling" the brain's reaction to stress.
Note the decrease in emotional range that often results from selective serotonin reuptake inhibitors. An effective antidepressant need not have this characteristic."Repetition of the restraint stress daily for 3 weeks totally abolished the effect of the stress on variations of 5-HT-moduline tissue content in all the studied brain regions. These results show that an acute restraint stress induces a rapid and significant increase in the amount of 5-HT-moduline contained in various brain areas. This phenomenon is likely to be related to the stress-induced 5-HT1B receptor desensitization which was previously demonstrated. (7)"
The brain responds to a consistently stressful environment by reducing the effects of 5-HT-moduline, or in the case of some antidepressant treatments, the SSRI. When someone taking a selective serotonin reuptake inhibitor ceases to take the drug, the 5-HT1b receptor regains its sensitivity, which would serve to enhance the effects of 5-HT-moduline. The withdrawal symptoms of SSRI's have been largely ignored by the drug companies producing them; they are in fact very real. Thus, SSRI's take advantage of a natural stress adaptation system in the brain. The ethical issues raised by this new understanding are extremely important in my opinion. The antibody for 5-HT-moduline seems to be the real cure that millions of people are seeking for anxiety related depression.
(1)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=11723184&loggedusing=M&Session=102188&SearchQuery=%22SB+216641%22&count=9
(2)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=10622374&loggedusing=M&Session=102188&SearchQuery=%225%2Dht%2Dmoduline%22&count=25
(3)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=11841572&loggedusing=M&Session=102188&SearchQuery=gaba+and+VTA+and+dopamine+and+accumbens&count=41
(4)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=29019305
(5)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=10372570&loggedusing=M&Session=&SearchQuery=%22Localization+of+brain+reinforcement+mechanisms%22&count=10
(6)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=10465699&loggedusing=M&Session=102188&SearchQuery=%225%2Dht%2Dmoduline%22&count=25
(7)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=10216182&loggedusing=M&Session=102188&SearchQuery=%225%2Dht%2Dmoduline%22&count=25
poster:Shawn. T.
thread:113825
URL: http://www.dr-bob.org/babble/20020725/msgs/114116.html