Posted by hawkeye on July 18, 2002, at 6:04:03
In reply to Re: enhancing and decreasing the same neurotransmitter, posted by cybercafe on July 17, 2002, at 2:44:16
RE:-->> "... another interesting effect is that if you take an antipsychotic and block a receptor, that leaves more dopamine available for the other receptors ... so the antipsychotic effectively increases the dopamine content in the synaps." <<--
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I remembered reading this excerpt from the book "Blaming ther Brain" and thought I'd pass it along. The book was published approx. 4 years ago and is authored by a Professor of Psychiatry at a major UK Medical School. In matters of the human psyche, nothing is simple."Another major problem for the theory that schizophrenia is caused by excessive dopamine activity is that antipsychotic drugs, as is also true of the antidepressants, generally take several weeks before they exhibit any significant therapeutic effect. This is true despite the fact that it has been demonstrated that the drugs block dopamine receptors in a matter of hours. After several weeks of drug treatment, there is a compensatory increase in the number of dopamine receptors and an increase in the firing rate of dopamine neurons. The increase in the number of receptors should increase the capacity of neurons to respond to dopamine, and when combined with an increase in firing rate of dopamine neurons and a consequent increase in the amount of dopamine released, dopamine activity might be expected to increase rather than decrease at the time that antipsychotic drugs first seem to be working-hardly a change that shouid correct excessive dopamine activity.
There have been some attempts to resolve this paradox by resorting to explanations based on what is known about the anatomical distribution of many D2 receptors. Many of the D2 receptors, which have been hypothesized to be critically involved in schizophrenia, are "autoreceptors." An "autoreceptor," which is located on the body of dopamine reieasing neurons, acts like a brake, slowing the firing rate of dopamine neurons and decreasing the amount of dopamine released. If these autoreceptors are blocked by a drug, it has the effect of removing a brake (or stepping on the gas pedal), and the neuron's firing rate is increased. As most antipsychotic drugs block D2 autoreceptors, this should produce an increase in the firing rate of dopamine neurons and an increase in the amount of dopamine released into synapses. Once again, a paradox appears, as an increase in the firing rate of dopamine neurons would seem to be just the opposite ofwhat a drug shouid do in order to alleviate a theorized dopamine hyperactivity.
In an attempt to resolve the paradox, it has been suggested that when neurons fire at an abnormaiiy high rate for about a three-week period, their celi membranes "depolarize." Depolarization refers to a reduction in the voìtage differential between the celi membrane and the cytopiasm within the neuron, a condition that biocks the ability of a neuron to fire and to release its transmitter. It has been reported in a recent study that the capacity of chronic administration of different antipsychotic drugs to produce depolarization block of dopamine neurons was reiated to their antipsychotic efflcacy in humans." depolarization effects of antipsychotic drugs believe that there is no reason to think that depolarization represents a return to the normal state of the dopamine system, and they conclude that there is probably nothing at all wrong with the dopamine system in schizophrenics."
http://digilander.libero.it/nopazzia/Valenstein/davalenstein.htm
poster:hawkeye
thread:112626
URL: http://www.dr-bob.org/babble/20020718/msgs/112748.html