Serotonin extracellular level

Ferre S, Artigas F (1995) Clozapine decreases serotonin extracellular levels in the nucleus accum-bens by a dopamine receptor-independent mechanism. Neurosci Lett 187 61 -4 Ferris CF, Melloni RH Jr, Koppel G, Perry KW, Fuller RW, Delville Y (1997) Vasopressin/ serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters. J Neurosci 17 4331 40... 

Iwakiri, H., Matsuyama, K. Mori, S. (1993). Extracellular levels of serotonin in the medial pontine reticular formation in relation to sleep-wake cycle in cats a microdialysis study. Neurosci. Res. 18, 157-70. 

Transporters for dopamine (DAT), serotonin (SERT) and norepinephrine (NET) are the initial targets for psychomotor stimulants. By interacting with these transporters (Chs 12 and 13), psychomotor stimulants increase extracellular levels of monoamine neurotransmitters. Cocaine is a monoamine uptake inhibitor. The reinforcing effects of cocaine correlate best with its binding potency at the DAT. However, experiments with monoamine transporter-deficient mice suggest that cocaine actions at... 

Monoamine reuptake inhibitors elevate extracellular levels of serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) in the brain by binding to one or more of the transporters responsible for reuptake, namely the serotonin transporter (SERT), the norepinephrine transporter (NET) and the dopamine transporter (DAT), thereby blocking the reuptake of the neurotransmitter(s) from the synaptic cleft [1], Monoamine reuptake inhibitors are an established drug class that has proven utility for the treatment of a number of CNS disorders, especially major depressive disorder (MDD). 

Stolerman IP, Chamberlain S, Bizarro L, Fernandes C, Schalkwyk L (2004) The role of nicotinic receptor alpha7 subunits in nicotine discrimination. Neuropharmacology 46 363-371 Summers KL, Giacobini E (1995) Effects of local and repeated systemic administration of (—) nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex. Neurochem Res 20 753-759... 

Ultimately, the effects of virtually aU existing antidepressants can be traced to the improvement of neurotransmission in the brain by one or more monoamine neurotransmitters, that is serotonin (5-HT, 4), norepinephrine (NE, 5), and dopamine (DA, 6). By blocking monoamine transporters, which remove the neurotransmitter from the synapse and extracellular space by uptake processes, the drugs increase extracellular levels of the transmitter and cause a cascade of intracellular events leading to the desired CNS effect. 

The discovery that drugs elevating extracellular levels of noradrenaline and/or serotonin have analgesic potential was circumstantial. In I960, Paoli et al. reported that during an attempt to treat reactive depression in chronic pain patients with the tricyclic antidepressant imipramine they observed an improvement of the patients neuralgic pain. Subsequently, it became well established that antidepressant drugs can improve both depression and chronic pain states. 

Bonvento G, Scatton B, Claustre Y, Rouquier L. Effect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on extracellular levels of serotonin in serotoneigic projection areas in the rat brain. Neurosci Lett 1992 137 101-104. 

In an attempt to shed light on the mechanism by which neuroleptics induce extrapyramidal reactions, Bishnoi et al. (2007) chronically administered haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) to rats, resulting in a time-dependent increase in orofacial hyperkinetic movements. They found a corresponding time-dependent decrease in extracellular levels of norepinephrine, dopamine, and serotonin in various cortical and subcortical regions of the brain. 

Depression, associated with reduced levels of the neurotransmitter serotonin (Figure 17.2). Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression. SSRIs increase the extracellular level of serotonin by inhibiting its reuptake into the presynaptic cell, thereby increasing its availability to the postsynaptic receptor. 

Bymaster, ER, Zhang, W., Carter, R, Shaw, J., Chernet, E., Rhebus, L., Wong, D. and Rerry, K.W. (2002) Eluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl), 160 353-61. 

Norepinephrine (NE) is a major neurotransmitter in both the central and peripheral nervous system and is involved in regulation of a variety of body functions. Extracellular levels of norepinephrine can be increased by blocking its reuptake by the norepinephrine transporter (NET). Drugs that inhibit norepinephrine reuptake either selectively or in combination with serotonin or dopamine have demonstrated efficacy in the clinic for a variety of indications such as attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), pain disorders (e.g. fibromyalgia), and vasomotor symptoms (VMS). In an effort to identify new selective NRIs, we designed a novel class of 1-(3-amino-1-phenylpropyl)indolin-2-ones. These compounds showed potency inhibiting NE reuptake when tested in the human norepinephrine transporter (hNET) inhibition assay. The compounds also showed selectivity (>100) against the human serotonin and dopamine transporters. The synthesis and properties of these novel compounds are described. 

Wilkinson, L. O., Auerbach, S. B. Jacobs, B. L. (1991). Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia. 

Kankaanpaa, A., Meririnne, E., Lillsunde, P., and Seppala, T., The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens, Pharmacol. Biochem. Behav. 59(4), 1003-1009, 1998. 

Hall, F.S., Devries, A.C., Fong, G.W., Huang, S., and Pert, A., Effects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels on extracellular serotonin in the striatum assessed with in vivo microdialysis relationship to behavior, Synapse 33(1), 16-25, 1999. 

Caffeine increases extracellular serotonin levels in the hippocampus (Okada et al. 1999). Enhanced release of dopamine and norepinephrine occurs at higher doses (Morgan and Vestal 1989). An inhibition of monoamine reuptake occurs, but only in the millimolar range, which would not matter at normal oral doses (Reith et al. 1987). 

Lumb AB. (1994). Effect of dried ginger on human platelet function. Thromb Haemost. 71(1) 110-1. Maione S, Palazzo E, Pallotta M, Leyva J, Berrino L, Rossi F. (1997). Effects of imipramine on raphe nuclei and prefrontal cortex extracellular serotonin levels in the rat. Psychopharmacology (Berlin). 134(4) 401-5. 

Watts VJ, Lawler CP, Fox DR, Neve KA, Nichols DE, Mailman RB. (1995). LSD and structural analogs pharmacological evaluation at D1 dopamine receptors. Psychopharmacology (Berlin). 118(4) 401-9. Wei D, Maisonneuve IM, Kuehne ME, Glick SD. (1998). Acute iboga alkaloid effects on extracellular serotonin (5-HT) levels in nucleus accumbens and striatum in rats. Brain Res. 800(2) 260-68. 

Role of extracellular serotonin levels in the effect of 5-HTlB receptor blockade. Psychopharmacology (Berl) 167(2) 153-158. 

Sizemore GM, Co C, Smith JE. 2000. Ventral pallidal extracellular fluid levels of dopamine, serotonin, gamma amino butyric acid, and glutamate during cocaine selfadministration in rats. Psychopharmacology (Berl) 150(4) 391-398. 

Some transmitters, including noradrenaline, dopamine, serotonin, and various neuropeptides, are sometimes called neuromodulators rather than neurotransmitters. These compounds may not initiate a nerve impulse but may act on adenylate cyclase to increase or decrease cAMP levels and protein kinase activity. They may also diffuse through the extracellular space to influence a region of the brain greater than a single synaptic cleft. However, the distinction between transmitters and modulators is not exact. 

Okada M, Kawata Y, Kiryu K, Mizuno K, Wada K, Tasaki H, Kaneko S (1997) Effects of adenosine receptor subtypes on hippocampal extracellular serotonin level and serotonin reuptake activity. J Neurochem 69(6) 2581-2588... 

---