Diphenyl diselenide decreases the prevalence of vacuous chewing movements induced by fluphenazine in rats.
BACKGROUND
Chronic treatment with neuroleptics causes, as a side effect, tardive dyskinesia in humans; however, the mechanisms involved in its pathophysiology remain unclear.


OBJECTIVE
The purpose of this study was to examine the effects of diphenyl diselenide, an organoselenium compound with antioxidant properties, in an animal model of vacuous chewing movements (VCMs) induced by long-term treatment with fluphenazine.


RESULTS
Adult male rats were treated during 24 weeks with fluphenazine (25 mg/kg, intramuscularly [i.m.], once every 21 days) and diphenyl diselenide (1 mg/kg, subcutaneously, three times a week). VCMs and body weight gain were quantified every 3 weeks. The fluphenazine treatment produced VCMs in the majority of the treated rats (87% after 24 weeks). Concomitant treatment with diphenyl diselenide decreased the prevalence of VCMs to 50%. Additionally, we separated the rats that developed or did not develop VCMs. We did not find any statistical differences among the groups when oxidative stress parameters were evaluated. Chronic fluphenazine treatment significantly decreased [(3)H]-dopamine uptake. Concomitant treatment with diphenyl diselenide was not able to prevent this decrease in those rats that developed VCMs.


CONCLUSIONS
Our data suggest that the reduction in dopamine transport can be a possible mechanism related to the maintenance of VCMs in rats. Moreover, diphenyl diselenide seems to be a promising pharmacological agent in the reduction in the prevalence of VCMs in rats.
Fachinetto
Roselei
R
Departamento de Química, Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
Villarinho
Jardel G
JG
Wagner
Caroline
C
Pereira
Romaiana P
RP
Puntel
Robson L
RL
Paixão
Márcio W
MW
Braga
Antonio L
AL
Calixto
João Batista
JB
Rocha
João B T
JB
Ferreira
Juliano
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001522:Behavior, Animal / Q000187:drug effects; D001555:Benzene Derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000503:physiopathology; D005476:Fluphenazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D008409:Mastication / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D014150:Antipsychotic Agents; D001555:Benzene Derivatives; D018492:Dopamine Antagonists; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; C017610:fluphenazine enanthate; D005476:Fluphenazine; D004298:Dopamine