title: Activation of adenosine A₂A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation.
abstract: BACKGROUND
  Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to pleasurable stimuli, and these USVs are considered a tool for investigating reward and motivation.
  
  
  OBJECTIVE
  This study aimed to clarify how activity of adenosine A2A receptors, which modulate reward and motivation, influences 50-kHz USV emission in rats.
  
  
  METHODS
  Rats received one of the following treatments in a test cage: (1) acute administration of the A2A receptor agonist CGS 21680 (0.05-0.2 mg/kg, i.p.) during social interactions; (2) long-term amphetamine (1 or 2 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.) administration on alternate days, alone or with CGS 21680, followed after 7 days of discontinuation by test cage re-exposure, to assess drug-conditioning effects, and thereafter drug challenge; (3) acute administration of the D1/D2 receptor agonist apomorphine (4 mg/kg, i.p.), alone or with CGS 21680; and (4) long-term administration of the non-selective A1/A2A receptor antagonist caffeine (15 mg/kg, i.p.), on alternate days. USVs and locomotor activity were evaluated throughout the treatments.
  
  
  RESULTS
  CGS 21680 attenuated 50-kHz USV emission stimulated by social interactions, amphetamine, apomorphine, and morphine, and rats administered CGS 21680 with amphetamine or morphine emitted fewer conditioned 50-kHz USVs upon test cage re-exposure, compared with rats administered amphetamine or morphine alone. Moreover, CGS 21680 administration prevented long-term changes in locomotor activity in amphetamine- and morphine-treated rats. Finally, caffeine had no effect on 50-kHz USVs.
  
  
  CONCLUSIONS
  These results indicate that activation of A2A receptors attenuates 50-kHz USV emission in rats and further elucidate how these receptors modulate the motivational properties of natural and pharmacological stimuli.
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale, 72, 09124, Cagliari, Italy. nicola.simola@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Simola
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale, 72, 09124, Cagliari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Costa
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale, 72, 09124, Cagliari, Italy.|CNR, National Research Council of Italy, Neuroscience Institute, Cagliari, Italy.
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D007398:Interpersonal Relations; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009042:Motivation / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects*; D012201:Reward; D012919:Social Behavior; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D009294:Narcotics; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002110:Caffeine; D009020:Morphine; D000661:Amphetamine; D000241:Adenosine; D001058:Apomorphine
keywords: Amphetamine; Apomorphine; CGS 21680; Caffeine; Morphine; Sensitization