Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats
| Autor: | Philippe De Deurwaerdère, Massimo Pierucci, Giuseppe Di Giovanni, Gabriele Deidda, Maurizio Casarrubea, Emilie Puginier, Julien Manem, Marta Ramos, Eleonora Cuboni, Rahul Bharatiya, Abdeslam Chagraoui |
|---|---|
| Přispěvatelé: | De Deurwaerdere P., Ramos M., Bharatiya R., Puginier E., Chagraoui A., Manem J., Cuboni E., Pierucci M., Deidda G., Casarrubea M., Di Giovanni G. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Serotonin Dopamine Substantia nigra Striatum Nucleus accumbens Settore BIO/09 - Fisiologia Lorcaserin Intracerebral microdialysis Rats Sprague-Dawley Dose-Response Relationship 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Single cell extracellular recordings Reward Internal medicine Receptor Serotonin 5-HT2C medicine Animals 5-HT2C Obesity Pharmacology Dose-Response Relationship Drug Pars compacta Chemistry Dopaminergic Neurons Dopaminergic Brain Neurochemistry Benzazepines Serotonin2C receptor Rats Ventral tegmental area 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Sprague-Dawley Drug Serotonin 5-HT2 Receptor Agonists Intracerebral microdialysi 030217 neurology & neurosurgery medicine.drug Receptor |
| Popis: | Lorcaserin, which is a selective agonist of serotonin2C receptors (5-HT2CRs), is a new FDA-approved anti-obesity drug that has also shown therapeutic promise in other brain disorders, such as addiction and epilepsy. The modulation of dopaminergic function might be critical in the therapeutic effect of lorcaserin, but its exact effect is unknown. Here, we studied the effect of the peripheral administration of lorcaserin on the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) dopaminergic neural activity, dopamine (DA) dialysis levels in the nucleus accumbens and striatum and on DA tissue levels in 29 different rat brain regions. Lorcaserin (5–640 μg/kg, i.v.) moderately inhibited only a subpopulation of VTA DA neurons, but had no effect on the SNc neurons. Lorcaserin (0.3, 3 mg/kg, i.p.) did not change VTA and SNc DA population neural activity but slightly decreased the firing rate and burst firing of the spontaneously active VTA neurons, without altering DA extracellular dialysate levels in both the nucleus accumbens and the striatum. Quantitative analysis of DA and metabolites tissue contents of the 29 areas studied revealed that lorcaserin (0.3 or 3 mg/kg, i.p.) only affected a few brain regions, i.e., increased DA in the central amygdala, ventral hypothalamus and nucleus accumbens core and decreased it in the ventromedial striatum. On the other hand, lorcaserin dramatically changed the direction and reduced the number of correlations of DA tissue content among several brain areas. These effects on DA terminal networks might be significant in the therapeutic mechanism of lorcaserin. This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|