title: Amphetamine-induced appetitive 50-kHz calls in rats: a marker of affect in mania?
abstract: BACKGROUND
  Animal models aimed to mimic mania have in common the lack of genuine affective parameters. Although rodent amphetamine-induced hyperlocomotion is a frequently used behavioral model of mania, locomotor activity is a rather unspecific target for developing new pharmacological therapies, and does not necessarily constitute a cardinal symptom in bipolar disorder (BD). Hence, alternative behavioral markers sensitive to stimulants are required.
  
  
  OBJECTIVE
  Since D-amphetamine induces appetitive 50-kHz ultrasonic vocalizations (USV) in rats, we asked whether established or potential antimanic drugs would inhibit this effect, thereby possibly complementing traditional analysis of locomotor activity.
  
  
  METHODS
  Amphetamine-treated rats (2.5 mg/kg) were systemically administered with the antimanic drugs lithium (100 mg/kg) and tamoxifen (1 mg/kg). Since protein kinase C (PKC) activity has been implicated in the pathophysiology of bipolar disorder and the biochemical effects of mood stabilizers, the new PKC inhibitor myricitrin (10, 30 mg/kg) was also evaluated.
  
  
  RESULTS
  We demonstrate for the first time that drugs with known or potential antimanic activity were effective in reversing amphetamine-induced appetitive 50-kHz calls. Treatments particularly normalized amphetamine-induced increases of frequency-modulated calls, a subtype presumably indicative of positive affect in the rat.
  
  
  CONCLUSIONS
  Our findings suggest that amphetamine-induced 50-kHz calls might constitute a marker for communicating affect that provides a useful model of exaggerated euphoric mood and pressured speech. The antimanic-like effects of the PKC inhibitors tamoxifen and myricitrin support the predictive and etiological validity of both drugs in this model and highlight the role of PKC signaling as a promising target to treat mania and psychosis-related disorders.
authors.affiliation: Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81540-990, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pereira
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
authors.forename: Rainer K W
authors.initials: RK
authors.lastname: Schwarting
authors.forename: Juan C
authors.initials: JC
authors.lastname: Brenes
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D016651:Lithium Carbonate / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D005419:Flavonoids; D013629:Tamoxifen; D016651:Lithium Carbonate; C008577:myricitrin; D011493:Protein Kinase C; D003913:Dextroamphetamine