2024-03-28T11:35:53Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1771022022-06-01T12:30:30Zcom_10261_105com_10261_1col_10261_358
http://hdl.handle.net/10261/177102
10.1016/j.neuropharm.2018.09.004
356958
Reduced cortical serotonin 5-HT2A receptor binding and glutamate activity in high compulsive drinker rats
Elsevier
2018
artículo
Mora, Santiago
Merchán, Ana
Vilchez, Olga
Aznar, Susana
Klein, Anders Bue
Ultved, Lene
Campa, Leticia
Suñol, Cristina
rp14695
Flores, Pilar
Moreno, Margarita
Compulsivity
Schedule-induced polydipsia
Serotonin
Glutamate
5-HT2A receptor
Prefrontal cortex
2018-12
Serotonin2A receptors and glutamate signaling have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by excessive drinking under intermittent food reinforcement schedules, is a valid model for studying the compulsive phenotype in rats. We explored the expression, function, and neurochemistry of 5-HT2A receptors in the frontal cortex (FC) of rats with individual differences to compulsivity. Rats were selected for high (HD) versus low (LD) drinking on SIP. First, we measured 5-HT2A, 5-HT1A, and mGlu2/3 receptors and serotonin transporter binding in different brain regions. Second, we assessed the effect of microinfusion into the medial prefrontal cortex (mPFC) of the 5-HT2A/C receptor agonist DOI, the mGlu2/3 agonist LY379268, and the combination of DOI with the 5-HT2A receptor antagonist M100907 and the 5-HT2C receptor antagonist SB242084. Finally, we measured the serotonin and glutamate efflux in mPFC in basal condition and after DOI local application. The compulsive HD rats showed a specific reduction of 5-HT2A receptor binding in FC compared to LD rats. The highest dose of DOI reduced compulsive drinking in HD rats on SIP, whereas LY379268 did not induce any significant effect. The 5-HT2A receptor antagonist M100907 reversed the DOI induced reduction on compulsive drinking in HD rats while blocking the 5-HT2C receptor did not affect SIP. Compulsive HD rats showed increased serotonin and decreased glutamate efflux in basal conditions that were modified by the DOI application. These findings indicate that reduced 5-HT2A receptor binding and glutamate neurochemical mechanisms may underlie compulsive behavior vulnerability.
Ministerio de Economía y Competitividad (España)
European Commission
Generalitat de Catalunya
Neuropharmacology
2018
143
10
19