title: Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned Effects of Amphetamine on Rat 50 kHz Ultrasonic Vocalizations.
abstract: BACKGROUND
  Rats emit 50 kHz ultrasonic vocalizations (USVs) in response to either natural or pharmacological pleasurable stimuli, and these USVs have emerged as a new behavioral measure for investigating the motivational properties of drugs. Earlier studies have indicated that activation of the dopaminergic system is critically involved in 50 kHz USV emissions. However, evidence also exists that non-dopaminergic neurotransmitters participate in this behavioral response.
  
  
  METHODS
  To ascertain whether glutamate transmission plays a role in 50 kHz USV emissions stimulated by amphetamine, rats received five amphetamine (1-2mg/kg, i.p.) administrations on alternate days in a test cage, either alone or combined with the glutamate N-methyl-D-aspartate receptor antagonist MK-801 (0.1-0.5mg/kg, i.p.). Seven days after treatment discontinuation, rats were re-exposed to the test cage to assess drug conditioning, and afterwards received a drug challenge. USVs and locomotor activity were evaluated, along with immunofluorescence for Zif-268 in various brain regions and spontaneous alternation in a Y maze.
  
  
  RESULTS
  Amphetamine-treated rats displayed higher 50 kHz USV emissions and locomotor activity than vehicle-treated rats, and emitted conditioned vocalizations on test cage re-exposure. Rats co-administered amphetamine and MK-801 displayed lower and dose-dependent 50 kHz USV emissions, but not lower locomotor activity, during repeated treatment and challenge, and scarce conditioned vocalization compared with amphetamine-treated rats. These effects were associated with lower levels of Zif-268 after amphetamine challenge and spontaneous alternation deficits.
  
  
  CONCLUSIONS
  These results indicate that glutamate transmission participates in the acute, long-term, and conditioned effects of amphetamine on 50 kHz USVs, possibly by influencing amphetamine-induced long-term neuronal changes and/or amphetamine-associated memories.
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Italy (Drs Costa, Morelli, and Simola); CNR, National Research Council of Italy, Neuroscience Institute, Cagliari, Italy (Dr Morelli).
authors.forename: Giulia
authors.initials: G
authors.lastname: Costa
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Italy (Drs Costa, Morelli, and Simola); CNR, National Research Council of Italy, Neuroscience Institute, Cagliari, Italy (Dr Morelli).
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Italy (Drs Costa, Morelli, and Simola); CNR, National Research Council of Italy, Neuroscience Institute, Cagliari, Italy (Dr Morelli). nicola.simola@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Simola
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000697:Central Nervous System Stimulants; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000661:Amphetamine
keywords: MK-801; Zif-268; psychostimulant; reward; sensitization; spontaneous alternation