TY - JOUR
T1 - Co-administration of progabide inhibits haloperidol-induced oral dyskinesias in rats
AU - Kaneda, Hiroyuki
AU - Shirakawa, Osamu
AU - Dale, James
AU - Goodman, Leslie
AU - Bachus, Susan E.
AU - Tamminga, Carol A.
PY - 1992/2/25
Y1 - 1992/2/25
N2 - Vacuous chewing movements in rats may be an animal analogue of the human motor disorder, tardive dyskinesia. The movements are phenomenologically and pharmacologically similar to tardive dyskinesia. The pathophysiology of these involuntary oral movements, and perhaps of tardive dyskinesia, are likely to include both dopamine receptor changes, and alterations in GABA (γ-aminobutyric acid) system function. In an attempt to test the involvement of GAVA system dysfunction in these movements, we treated rats chronically with water alone, haloperidol alone, the GABA agonist progabide alone, and haloperidol plus progabide. Sprague-Dawley rats received haloperidol (1.5 mg/kg per day) in their drinking water and progabide (100 mg/kg per day) in their food for 12 months. After 12 months of treatment, haloperidol had induced vacuous chewing movements when administered alone, but the prevalence of the movements was decreased by 40% with the coadministration of progabide. Moreover, the haloperidol-progabide-treated animals did not merely demonstrate movement suppression but actual inhibition of movement onset, as determined by an additional progabide-withdrawal experiment. These data would suggest that progabide and perhaps other GABAmimetic compounds can prevent the development of tarkive dyskinesia in man.
AB - Vacuous chewing movements in rats may be an animal analogue of the human motor disorder, tardive dyskinesia. The movements are phenomenologically and pharmacologically similar to tardive dyskinesia. The pathophysiology of these involuntary oral movements, and perhaps of tardive dyskinesia, are likely to include both dopamine receptor changes, and alterations in GABA (γ-aminobutyric acid) system function. In an attempt to test the involvement of GAVA system dysfunction in these movements, we treated rats chronically with water alone, haloperidol alone, the GABA agonist progabide alone, and haloperidol plus progabide. Sprague-Dawley rats received haloperidol (1.5 mg/kg per day) in their drinking water and progabide (100 mg/kg per day) in their food for 12 months. After 12 months of treatment, haloperidol had induced vacuous chewing movements when administered alone, but the prevalence of the movements was decreased by 40% with the coadministration of progabide. Moreover, the haloperidol-progabide-treated animals did not merely demonstrate movement suppression but actual inhibition of movement onset, as determined by an additional progabide-withdrawal experiment. These data would suggest that progabide and perhaps other GABAmimetic compounds can prevent the development of tarkive dyskinesia in man.
KW - Haloperidol (chronic)
KW - Progabide
KW - Tardive dyskinesia
KW - Vacuous chewing movements
UR - http://www.scopus.com/inward/record.url?scp=0026502737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026502737&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(92)90070-K
DO - 10.1016/0014-2999(92)90070-K
M3 - Article
C2 - 1555638
AN - SCOPUS:0026502737
SN - 0014-2999
VL - 212
SP - 43
EP - 49
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -