Neuroscience
Move over, melanocortin receptors, 5-HT4 receptors are ready to take your place. Agonists of the 5-HT4 receptor, a subtype of the serotonin receptor family, seem to do the following, according to recently published reports:
(1) mediate the appetite-suppressing qualities of ecstasy (MDMA), and supposedly the self-reinforcing qualities of starving for individuals with anorexia nervosa (Jean et al., 2007). This paper was the one in PNAS mentioned the other day by The Neurocritic.
Fig. 1 (Lezoualc'h, 2007). In vivo and in vitro evidence for a beneficial effect of 5-HT4 receptor agonists in AD. 5-HT4 agonists facilitate ACh [acetylcholine] release in rat frontal and hippocampus and modulate different aspects of memory performance in behavioural experiments. In addition, they increase the extracellular release of sAPPα [non-amyloidogenic soluble form of APP] and decrease Aβ [amyloid β-peptide] secretion in primary neurons. sAPPα has potent memory-enhancing effects and displays neuroprotective and neurotrophic properties.
The one major thing the MC4R subtype of melanocortin receptors has over 5-HT4R is its potential as an aphrodisiac, in the form of PT-141 (company press release and PDF).
References
Alexandra Jean, Grégory Conductier, Christine Manrique, Constantin Bouras, Philippe Berta, René Hen, Yves Charnay, Joël Bockaert, and Valérie Compan (2007). Anorexia induced by activation of serotonin 5-HT4 receptors is mediated by increases in CART in the nucleus accumbens. PNAS published online October 3, 2007.
Lezoualc'h F. (2007). 5-HT4 receptor and Alzheimer's disease: the amyloid connection. Exp Neurol. 205:325-9.
Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S, Lambas-Senas L, Wiborg O, Haddjeri N, Pineyro G, Sadikot AF, Debonnel G. (2007 ). Serotonin-4 (5HT-4) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55:712-25.
Maillet M, Robert SJ, Lezoualc'h F. (2004). New insights into serotonin 5-HT4 receptors : a novel therapeutic target for Alzheimer's disease? Curr Alzheimer Res. 1(2):79-85.
- D1 Receptor Knock-out Mice Say, "no Cocaine For Us!"
"However, we'll still take plenty of food and opioid agonists!" Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine: Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob...
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The Agony of Genetically Disrupted Melanocortin Receptors (MC4R). A new study suggests that blocking MC4R function in the central nervous system of rodents produces obesity by altering lipid metabolism and promoting fat deposition (Nogueiras et al.,...
- The Joy Of Melanocortin Receptors
Lose Weight and Improve Your Sex Life! Those two pitches account for approximately 95% of all spam, right? But what if you could manufacture one drug that promises to do both things? Think of the profits!! Although it sounds too good to be true, there...
- Neuropsychology Abstract Of The Day: Sorl1 And Alzheimer Disease
Ekaterina Rogaeva, Yan Meng, Joseph H Lee, Yongjun Gu, Toshitaka Kawarai, et al. (2007). The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature Genetics, Published online: 14 January 2007; | doi:10.1038/ng1943....
- Af267b And Alzheimer Disease
From medicalnewstoday.com:Experimental Drug Reverses Key Cognitive Deficits, Pathology In Alzheimer's Main Category: Alzheimer's News Article Date: 04 Mar 2006 - 13:00pm (UK) A new drug that enhances the activity of a key brain cell receptor...
Neuroscience
The Joy of 5-HT4 Receptors
Move over, melanocortin receptors, 5-HT4 receptors are ready to take your place. Agonists of the 5-HT4 receptor, a subtype of the serotonin receptor family, seem to do the following, according to recently published reports:
(1) mediate the appetite-suppressing qualities of ecstasy (MDMA), and supposedly the self-reinforcing qualities of starving for individuals with anorexia nervosa (Jean et al., 2007). This paper was the one in PNAS mentioned the other day by The Neurocritic.
We [Jean et al., 2007] hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of 5-HT4R in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. ... Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of MDMA involve the 5-HT4R. Using 5-HT4R knockout mice, we demonstrate that 5-HT4R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. ...(2) act as a rapid-onset antidepressant (Lucas et al., 2007); no more waiting 3-6 weeks for treatment response from those pesky SSRIs. In a rodent model of depression, acute administration of 5-HT4 agonists was more effective than citalopram in reducing immobility in the forced swimming test.
Moreover, a 3 day regimen with such compounds modifies rat brain parameters considered to be key markers of antidepressant action, but that are observed only after 2–3 week treatments with classical molecules: desensitization of 5-HT1A receptors, and enhanced phosphorylation of the CREB protein and neurogenesis in the hippocampus. In contrast, a 3 day treatment with the SSRI citalopram remains devoid of any effect on these parameters.(3) improve memory and affect amyloid metabolism (Lezoualc'h, 2007), making it a possible target for drugs to treat Alzheimer's disease (Maillet et al., 2004).
Fig. 1 (Lezoualc'h, 2007). In vivo and in vitro evidence for a beneficial effect of 5-HT4 receptor agonists in AD. 5-HT4 agonists facilitate ACh [acetylcholine] release in rat frontal and hippocampus and modulate different aspects of memory performance in behavioural experiments. In addition, they increase the extracellular release of sAPPα [non-amyloidogenic soluble form of APP] and decrease Aβ [amyloid β-peptide] secretion in primary neurons. sAPPα has potent memory-enhancing effects and displays neuroprotective and neurotrophic properties.
The one major thing the MC4R subtype of melanocortin receptors has over 5-HT4R is its potential as an aphrodisiac, in the form of PT-141 (company press release and PDF).
References
Alexandra Jean, Grégory Conductier, Christine Manrique, Constantin Bouras, Philippe Berta, René Hen, Yves Charnay, Joël Bockaert, and Valérie Compan (2007). Anorexia induced by activation of serotonin 5-HT4 receptors is mediated by increases in CART in the nucleus accumbens. PNAS published online October 3, 2007.
Lezoualc'h F. (2007). 5-HT4 receptor and Alzheimer's disease: the amyloid connection. Exp Neurol. 205:325-9.
Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S, Lambas-Senas L, Wiborg O, Haddjeri N, Pineyro G, Sadikot AF, Debonnel G. (2007 ). Serotonin-4 (5HT-4) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55:712-25.
Maillet M, Robert SJ, Lezoualc'h F. (2004). New insights into serotonin 5-HT4 receptors : a novel therapeutic target for Alzheimer's disease? Curr Alzheimer Res. 1(2):79-85.
- D1 Receptor Knock-out Mice Say, "no Cocaine For Us!"
"However, we'll still take plenty of food and opioid agonists!" Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine: Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob...
- I'm Not As Slim As That Mouse
The Agony of Genetically Disrupted Melanocortin Receptors (MC4R). A new study suggests that blocking MC4R function in the central nervous system of rodents produces obesity by altering lipid metabolism and promoting fat deposition (Nogueiras et al.,...
- The Joy Of Melanocortin Receptors
Lose Weight and Improve Your Sex Life! Those two pitches account for approximately 95% of all spam, right? But what if you could manufacture one drug that promises to do both things? Think of the profits!! Although it sounds too good to be true, there...
- Neuropsychology Abstract Of The Day: Sorl1 And Alzheimer Disease
Ekaterina Rogaeva, Yan Meng, Joseph H Lee, Yongjun Gu, Toshitaka Kawarai, et al. (2007). The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature Genetics, Published online: 14 January 2007; | doi:10.1038/ng1943....
- Af267b And Alzheimer Disease
From medicalnewstoday.com:Experimental Drug Reverses Key Cognitive Deficits, Pathology In Alzheimer's Main Category: Alzheimer's News Article Date: 04 Mar 2006 - 13:00pm (UK) A new drug that enhances the activity of a key brain cell receptor...