Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice
IntroductionStudies suggest that serotonin (5-HT) plays an important role in alcohol use disorder (AUD). While several receptor subtypes modulate the role of 5-HT in AUD, evidence suggests that 5-HT2A and 5-HT2C receptors may be directly involved in alcohol drinking due to their interaction with the...
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Frontiers Media S.A.
2025-08-01
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| author | Sandy C. Simões Livia N. Amorim Yasmim A. Serra Camila S. Abreu Maria Clara E. Santana João P. C. Leite Carla M. Kaneto Roberta C. A. Costa Kaio R. Ferreira Isabelle C. S. de Oliveira Alexandre J. Oliveira-Lima Agnieszka Sulima Kenner C. Rice Eduardo A. V. Marinho Lais F. Berro Lais F. Berro |
| author_facet | Sandy C. Simões Livia N. Amorim Yasmim A. Serra Camila S. Abreu Maria Clara E. Santana João P. C. Leite Carla M. Kaneto Roberta C. A. Costa Kaio R. Ferreira Isabelle C. S. de Oliveira Alexandre J. Oliveira-Lima Agnieszka Sulima Kenner C. Rice Eduardo A. V. Marinho Lais F. Berro Lais F. Berro |
| author_sort | Sandy C. Simões |
| collection | DOAJ |
| description | IntroductionStudies suggest that serotonin (5-HT) plays an important role in alcohol use disorder (AUD). While several receptor subtypes modulate the role of 5-HT in AUD, evidence suggests that 5-HT2A and 5-HT2C receptors may be directly involved in alcohol drinking due to their interaction with the mesolimbic dopaminergic system. The aim of the present study was to investigate the effects of 5-HT2A and 5-HT2C antagonists, alone or in combination, on the acquisition and expression (i.e., return to alcohol drinking after a period of abstinence/treatment) of voluntary alcohol drinking in male mice.MethodsAnimals had intermittent access to alcohol (10% v/v) in a two-bottle choice procedure for 30 days (acquisition), and were then submitted to alcohol re-exposure sessions after periods of abstinence. Vehicle, the 5-HT2A receptor antagonist M100907 (M100, 1 mg/kg) and/or the 5-HT2C receptor antagonist SB242084 (SB, 1 mg/kg) were administered either prior to acquisition (Experiment 1) or during the abstinence period preceding re-exposure sessions (Experiment 2). During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions.ResultsOur findings show that combined treatment with 5-HT2A and 5-HT2C antagonists, but not treatment with the antagonists separately, reduced alcohol drinking and preference when administered immediately before acquisition (Experiment 1). Combined treatment with 5-HT2A and 5-HT2C antagonists after the establishment of voluntary alcohol drinking did not alter the expression of drinking behavior (Experiment 2). On the other hand, while post-acquisition treatment with a 5-HT2A antagonist alone decreased alcohol intake and preference during re-exposure, co-administration of a 5-HT2C antagonist blocked these effects.DiscussionOur findings suggest that 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in mice. |
| format | Article |
| id | doaj-art-002b146c7a284e62840deb0e6fae0d52 |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-002b146c7a284e62840deb0e6fae0d522025-08-25T05:25:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-08-011910.3389/fnins.2025.16393441639344Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male miceSandy C. Simões0Livia N. Amorim1Yasmim A. Serra2Camila S. Abreu3Maria Clara E. Santana4João P. C. Leite5Carla M. Kaneto6Roberta C. A. Costa7Kaio R. Ferreira8Isabelle C. S. de Oliveira9Alexandre J. Oliveira-Lima10Agnieszka Sulima11Kenner C. Rice12Eduardo A. V. Marinho13Lais F. Berro14Lais F. Berro15Department of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, United StatesDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United StatesDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDepartment of Health Sciences, Universidade Estadual de Santa Cruz, Ilhéus, BrazilDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United StatesIntroductionStudies suggest that serotonin (5-HT) plays an important role in alcohol use disorder (AUD). While several receptor subtypes modulate the role of 5-HT in AUD, evidence suggests that 5-HT2A and 5-HT2C receptors may be directly involved in alcohol drinking due to their interaction with the mesolimbic dopaminergic system. The aim of the present study was to investigate the effects of 5-HT2A and 5-HT2C antagonists, alone or in combination, on the acquisition and expression (i.e., return to alcohol drinking after a period of abstinence/treatment) of voluntary alcohol drinking in male mice.MethodsAnimals had intermittent access to alcohol (10% v/v) in a two-bottle choice procedure for 30 days (acquisition), and were then submitted to alcohol re-exposure sessions after periods of abstinence. Vehicle, the 5-HT2A receptor antagonist M100907 (M100, 1 mg/kg) and/or the 5-HT2C receptor antagonist SB242084 (SB, 1 mg/kg) were administered either prior to acquisition (Experiment 1) or during the abstinence period preceding re-exposure sessions (Experiment 2). During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions.ResultsOur findings show that combined treatment with 5-HT2A and 5-HT2C antagonists, but not treatment with the antagonists separately, reduced alcohol drinking and preference when administered immediately before acquisition (Experiment 1). Combined treatment with 5-HT2A and 5-HT2C antagonists after the establishment of voluntary alcohol drinking did not alter the expression of drinking behavior (Experiment 2). On the other hand, while post-acquisition treatment with a 5-HT2A antagonist alone decreased alcohol intake and preference during re-exposure, co-administration of a 5-HT2C antagonist blocked these effects.DiscussionOur findings suggest that 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in mice.https://www.frontiersin.org/articles/10.3389/fnins.2025.1639344/fullalcoholserotonintwo-bottle choicemice5-HT2A5-HT2C |
| spellingShingle | Sandy C. Simões Livia N. Amorim Yasmim A. Serra Camila S. Abreu Maria Clara E. Santana João P. C. Leite Carla M. Kaneto Roberta C. A. Costa Kaio R. Ferreira Isabelle C. S. de Oliveira Alexandre J. Oliveira-Lima Agnieszka Sulima Kenner C. Rice Eduardo A. V. Marinho Lais F. Berro Lais F. Berro Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice Frontiers in Neuroscience alcohol serotonin two-bottle choice mice 5-HT2A 5-HT2C |
| title | Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| title_full | Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| title_fullStr | Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| title_full_unstemmed | Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| title_short | Serotonin 5-HT2A and 5-HT2C receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| title_sort | serotonin 5 ht2a and 5 ht2c receptors differentially modulate the acquisition and expression of voluntary alcohol drinking in male mice |
| topic | alcohol serotonin two-bottle choice mice 5-HT2A 5-HT2C |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1639344/full |
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