Posted by AndrewB on April 25, 2000, at 13:19:25
In reply to Beta Receptor Down-Regulation, posted by PeterJ on April 25, 2000, at 3:44:51
Peter,
Thank you Peter for your excellent explanation of beta receptor down-regulation. It seems that the physiological changes to neurotransmitter neurons due to down-regulation are used by researchers as evidence of increased neurotransmitter receptor stimulation when trying to determine the actions (direct or indirect) of a drug or another neurotransmitter.
I hope you can answer my questions, I’m wondering if tolerance to a drug ever occurs due to down-regulation. Specifically I’ve read that tolerance to amphetamines is due to down-regulation of the alpha and beta andrenergic receptors due constant innervation of the post synaptic receptors. But I also have read a contradicting explanation for amphetamine tolerance. This explanation says amphetamine promotes the release of NE from nerve endings, specifically the cytoplasmic stores of NE. Tolerance in this scenario develops because only a limited amount of NE is available in this ‘mobile pool’. Which of these explanations sounds correct?
I realize that with SSRIs you don’t need ever increasing doses, so whatever down-regulation they create doesn’t cause tolerance. However if you stop taking an SSRI, are some people going to feel more depressed than ever before because their serotonergic and adrenergic systems have been down-regulated.
The reason I’m asking these questions is because I am trying amineptine. It is a dopamine reuptake blocker and is classified as a mild psychostimulant. I am wary of any psychostimulant causing tolerance. Amineptine is able to sharpen one’s mind among other things, but today I have not taken amineptine and I feel foggy headed. My mind is less sharp than it was before I started amineptine. Is this fogginess due to down-regulation (of either the dopaminergic or NE system). Can drug holidays counteract tolerance. If so, is there any standard protocol for the timing and spacing of drug holidays.
Thank you very much,
AndrewB
poster:AndrewB
thread:30864
URL: http://www.dr-bob.org/babble/20000420/msgs/31228.html