Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors

Ethanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olf...

Full description

Bibliographic Details
Main Authors: Laura López-Cruz, Noemí San-Miguel, Pilar Bayarri, Younis Baqui, Christa Elisabeth Müller, John D Salamone, Merce Correa
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-11-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00206/full
_version_ 1817979871016517632
author Laura López-Cruz
Noemí San-Miguel
Pilar Bayarri
Younis Baqui
Christa Elisabeth Müller
John D Salamone
Merce Correa
author_facet Laura López-Cruz
Noemí San-Miguel
Pilar Bayarri
Younis Baqui
Christa Elisabeth Müller
John D Salamone
Merce Correa
author_sort Laura López-Cruz
collection DOAJ
description Ethanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olfactory tubercle, brain areas involved in exploration and social interaction in rodents. Ethanol modulates social interaction processes, but the role of adenosine in social behavior is still poorly understood. The present work was undertaken to study the impact of ethanol, caffeine and their combination on social behavior, and to explore the involvement of A1 and A2A receptors on those actions. Male CD1 mice were evaluated in a social interaction three-chamber paradigm, for preference of conspecific vs. object, and also for long-term recognition memory of familiar vs. novel conspecific. Ethanol showed a biphasic effect, with low doses (0.25 g/kg) increasing social contact and higher doses (1.0-1.5 g/kg) reducing social interaction. However, no dose changed social preference; mice always spent more time sniffing the conspecific than the object, independently of the ethanol dose. Ethanol, even at doses that did not change social exploration, produced amnestic effects on social recognition the following day. Caffeine reduced social contact (15.0-60.0 mg/kg), and even blocked social preference at higher doses (30.0-60.0 mg/kg). The A1 antagonist CPT (3-9 mg/kg) did not modify social contact or preference on its own, and the A2A antagonist MSX-3 (1.5-6 mg/kg) increased social interaction at all doses. Ethanol at intermediate doses (0.5-1.0 g/kg) was able to reverse the reduction in social exploration induced by caffeine (15.0-30.0 mg/kg). Although there was no interaction between ethanol and CPT or MSX-3 on social exploration in the first day, MSX-3 blocked the amnestic effects of ethanol observed on the following day. Thus, ethanol impairs the formation of social memories, and A2A adenosine antagonists can prevent the amnestic effects of ethanol, so that animals can recognice familiar conspecifics. On the other hand, ethanol can counteract the social withdrawal induced by caffeine, a non-selective adenosine A1/A2A receptor antagonist. These results show the complex set of interactions between ethanol and caffeine, some of which could be the
first_indexed 2024-04-13T22:47:40Z
format Article
id doaj.art-a4190043fe2a4d86a4086af54e8559f0
institution Directory Open Access Journal
issn 1662-5153
language English
last_indexed 2024-04-13T22:47:40Z
publishDate 2016-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Behavioral Neuroscience
spelling doaj.art-a4190043fe2a4d86a4086af54e8559f02022-12-22T02:26:20ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532016-11-011010.3389/fnbeh.2016.00206224160Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptorsLaura López-Cruz0Noemí San-Miguel1Pilar Bayarri2Younis Baqui3Christa Elisabeth Müller4John D Salamone5Merce Correa6Universitat Jaume IUniversitat Jaume IUniversitat Jaume IPharmazeutische Chemie, Pharmazeutisches Institut, Universität Bonn,Pharmazeutische Chemie, Pharmazeutisches Institut, Universität Bonn,University of ConnecticutUniversitat Jaume IEthanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olfactory tubercle, brain areas involved in exploration and social interaction in rodents. Ethanol modulates social interaction processes, but the role of adenosine in social behavior is still poorly understood. The present work was undertaken to study the impact of ethanol, caffeine and their combination on social behavior, and to explore the involvement of A1 and A2A receptors on those actions. Male CD1 mice were evaluated in a social interaction three-chamber paradigm, for preference of conspecific vs. object, and also for long-term recognition memory of familiar vs. novel conspecific. Ethanol showed a biphasic effect, with low doses (0.25 g/kg) increasing social contact and higher doses (1.0-1.5 g/kg) reducing social interaction. However, no dose changed social preference; mice always spent more time sniffing the conspecific than the object, independently of the ethanol dose. Ethanol, even at doses that did not change social exploration, produced amnestic effects on social recognition the following day. Caffeine reduced social contact (15.0-60.0 mg/kg), and even blocked social preference at higher doses (30.0-60.0 mg/kg). The A1 antagonist CPT (3-9 mg/kg) did not modify social contact or preference on its own, and the A2A antagonist MSX-3 (1.5-6 mg/kg) increased social interaction at all doses. Ethanol at intermediate doses (0.5-1.0 g/kg) was able to reverse the reduction in social exploration induced by caffeine (15.0-30.0 mg/kg). Although there was no interaction between ethanol and CPT or MSX-3 on social exploration in the first day, MSX-3 blocked the amnestic effects of ethanol observed on the following day. Thus, ethanol impairs the formation of social memories, and A2A adenosine antagonists can prevent the amnestic effects of ethanol, so that animals can recognice familiar conspecifics. On the other hand, ethanol can counteract the social withdrawal induced by caffeine, a non-selective adenosine A1/A2A receptor antagonist. These results show the complex set of interactions between ethanol and caffeine, some of which could be thehttp://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00206/fullAdenosineAnxietyEthanolSocial MemorySocial explorationcaffeine.
spellingShingle Laura López-Cruz
Noemí San-Miguel
Pilar Bayarri
Younis Baqui
Christa Elisabeth Müller
John D Salamone
Merce Correa
Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
Frontiers in Behavioral Neuroscience
Adenosine
Anxiety
Ethanol
Social Memory
Social exploration
caffeine.
title Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
title_full Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
title_fullStr Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
title_full_unstemmed Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
title_short Ethanol and Caffeine effects on social interaction and recognition in mice: Involvement of adenosine A2A and A1 receptors
title_sort ethanol and caffeine effects on social interaction and recognition in mice involvement of adenosine a2a and a1 receptors
topic Adenosine
Anxiety
Ethanol
Social Memory
Social exploration
caffeine.
url http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00206/full
work_keys_str_mv AT lauralopezcruz ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT noemisanmiguel ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT pilarbayarri ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT younisbaqui ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT christaelisabethmuller ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT johndsalamone ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors
AT mercecorrea ethanolandcaffeineeffectsonsocialinteractionandrecognitioninmiceinvolvementofadenosinea2aanda1receptors