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Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats

De Deurwaerdère, Philippe ; Ramos, Marta LU orcid ; Bharatiya, Rahul ; Puginier, Emilie ; Chagraoui, Abdeslam ; Manem, Julien ; Cuboni, Eleonora ; Pierucci, Massimo ; Deidda, Gabriele and Casarrubea, Maurizio , et al. (2020) In Neuropharmacology 166.
Abstract
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,... (More)
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’. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Neuropharmacology
volume
166
article number
107915
publisher
Elsevier
external identifiers
  • pmid:31862271
  • scopus:85078508811
ISSN
0028-3908
DOI
10.1016/j.neuropharm.2019.107915
language
English
LU publication?
no
id
5fe2a4d6-1483-4726-ba03-c3e705d8e4d7
alternative location
https://linkinghub.elsevier.com/retrieve/pii/S0028390819304861
date added to LUP
2021-01-25 11:02:10
date last changed
2022-08-18 14:17:32
@article{5fe2a4d6-1483-4726-ba03-c3e705d8e4d7,
  abstract     = {{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.<br/><br/>This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’.}},
  author       = {{De Deurwaerdère, Philippe and Ramos, Marta and Bharatiya, Rahul and Puginier, Emilie and Chagraoui, Abdeslam and Manem, Julien and Cuboni, Eleonora and Pierucci, Massimo and Deidda, Gabriele and Casarrubea, Maurizio and Di Giovanni, Giuseppe}},
  issn         = {{0028-3908}},
  language     = {{eng}},
  month        = {{04}},
  publisher    = {{Elsevier}},
  series       = {{Neuropharmacology}},
  title        = {{Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats}},
  url          = {{http://dx.doi.org/10.1016/j.neuropharm.2019.107915}},
  doi          = {{10.1016/j.neuropharm.2019.107915}},
  volume       = {{166}},
  year         = {{2020}},
}