Serotonin system

Jacobs, BL and Azmitia, EC (1992) Structure and function of the brain serotonin system. Physiol. Rev. 72 165-229. 

Chaput, Y, de Montigny, C and Blier, P (1991) Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 5 219-229. 

RESPONSE Yes, and there is some recent study too that was done by Lyness showing that if the serotonin system is destroyed, toxicity and seh-admirhstration of amphetamines are increased. There is a lot of evidence that some of this interaction does occur at some level, but we don t know where yet. 

COMMENT You have presented some evidence that dopamine may be involved in the neurotoxic action of methamphetamine in terms of dopaminergic neurons, and you presented evidence suggesting that it may be involved in not only the dopamine system but also the serotonin system. 

While brain serotonin systems may play a key role in mediating some of the effects of MDMA on analgesia and body temperature as well as in the reported anxiolytic-like and mood-altering subjective effects of the drug, additional neurotransmitter systems may contribute to some of the unique subjective experiences reported for MDMA and other drugs in this class. 

Wiklund, L., and Bjorklund, A. Mechanisms of regrowth in the bulbospinal serotonin system following 5,6-dihydroxytryptamine induced axotomy. 11. Fluorescence histochemical observations. Brain Res 191 129-160. 1980. 

So I think you can debate that issue about 99 or 95 percent depletion. I think that if you probe those animals with the proper pharmacological agents and proper environmental situation, you will pick up deficits. I think the lack of knowledge about what the serotonin systems do is the basis of the problem here. We don t know what the behavioral consequences of the serotonin depletion are. 

Gerra, G., Zaimovic, A., Ferri, M., Zambelli, U., Timpano, M., Neri, E., Marzocchi, G.F., Delsignore, R., and Brambilla, F., Long-lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans, Biol. Psychiatry 47(2), 127-136, 2000. 

Hong JS, Tilson HA, Uphouse LL, et al. 1984. Effects of chlordecone exposure on brain neurotransmitters Possible involvement of the serotonin system in chlordecone-elicited tremor. Toxicol Appl Pharmacol 73 336-344. 

Williams J, Eckols K, Stewart G, et al. 1988a. Proestrous effects of chlordecone on the serotonin system. Neurotoxicology 9 597-610. 

Buspirone does not share any of the problematic benzodiazepine properties such as sedation, motor impairment, addiction, physical dependence, or withdrawal. The most common side effects of buspirone include dizziness, nausea, headache, fatigue, and dry mouth. Despite its activity in the serotonin system, buspirone is not associated with the sexual side effects that plague the SSRIs, SNRIs, MAOIs, and TCAs. 

Gingrich JA, Hen R (2001) Dissecting the role of the serotonin system in nemopsychiatric disorders using knockout mice. Psychopharmacology (Berl) 155 1-10 Giorgo O, Corda MG, Carbon G, Frau V, Valentini V, Di Chiara G (1997) Effects of cocaine and morphine in rats from two psychogenetically selected rat lines a behavioral and brain dialysis study. Behav Genet 27 537-546... 

Functional Neuroanatomy of Emotionality Focus on the Serotonin System. 74... 

Blier P, de Montigny C (1998) Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 44 313-323 Bonasera SJ, Tecott LH (2000) Mouse models of serotonin receptor function toward agenetic dissection of serotonin systems. Pharmacol Ther 88 133-142 Bonhoeffer T (1996) Neurotrophins and activity-dependent development of the neocortex. Curr Opin Nemobiol 6 119-126... 

SERTPR variants may also not be specifically associated with response to SSRIs but confer a more general predisposition to respond to any kind of antidepressant treatment targeting the serotonin system. The 1 allele of SERTP R has not only associated been associated with a better response to SSRIs but also a good response to total sleep deprivation (Benedetti et al. 1999). An enhancement of serotonergic transmission has been proposed as one possible mechanism of action of sleep deprivation (Gardner et al. 1997). 

Mirtazapine (Remeron) enhances both serotonergic and noradrenergic neurotransmission. By blocking presynaptic aj-adrenoceptors, mirtazapine causes release of norepinephrine. Indirectly, through noradrenergic modulation of serotonin systems, mirtazapine also causes increased release of serotonin. It is an antagonist... 

Veenstra-VanderWeele, J., Anderson, G.M., and Cook, E.H. (2000) Pharmacogenetics and the serotonin system initial studies and future directions. Eur Pharmacol 410 165-181. 

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