Pro-Leu-glycinamide and its peptidomimetic, PAOPA, attenuate haloperidol induced vacuous chewing movements in rat: A model of human tardive dyskinesia.
In the present experimental paradigm, we examine the effect of L-prolyl-L-leucyl-glycinamide (PLG) co-administration with haloperidol on vacuous chewing movements (VCM) in rats-a model of tardive dyskinesia (TD) in humans. We examined the dose dependent induction of VCM through both injected and orally administered PLG (MIF-1). Our results show significant levels of VCM attenuation (P<0.05) in rats treated with 10mg/kg of PLG. Doses of 1 and 100mg/kg were ineffective. Reductions were present in both orally treated and injected rats. We also examined the therapeutic effect of a peptidomimetic of PLG-PAOPA. PAOPA was able to produce similar behavioral effects to PLG at a dose, which was 100-fold lower than the effective dose of PLG. These results suggest that PLG may play a role in D2 receptor expression and function, as well as providing a therapy for neuroleptic induced TD.
Sharma
S
S
Department of Psychiatry, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Ont., L8N 3Z5, Hamilton, Canada.
Paladino
P
P
Gabriele
J
J
Saeedi
H
H
Henry
P
P
Chang
M
M
Mishra
R K
RK
Johnson
R L
RL
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D006220:Haloperidol / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D006801:Humans; D007267:Injections; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D008409:Mastication / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D011760:Pyrrolidinones; C067487:3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide; D009075:MSH Release-Inhibiting Hormone; D006220:Haloperidol