Modulatory effects of PLG and its peptidomimetics on haloperidol-induced catalepsy in rats.
A behavioral model of dopaminergic function in the rat was used to examine the anticataleptic effects of L-prolyl-L-leucyl-glycinamide (PLG) and peptidomimetic analogs of PLG. Administration of 1 mg/kg PLG intraperitoneally significantly attenuated haloperidol (1 mg/kg)-induced catalepsy (as measured by the standard horizontal bar test), whereas doses of 0.1 and 10 mg/kg PLG did not. Eight synthetic PLG peptidomimetics (Calpha, alpha-dialkylated glycyl residues with lactam bridge constraint [1-4] and without [5-8]) were tested in the same manner (at a dose of 1 microg/kg) and categorized according to their activity, i.e. very active (5), moderately active (2, 3, 4, and 6), and inactive (1, 7, and 8). The catalepsy-reversal action of the diethylglycine-substituted peptidomimetic 5 was examined further and found to exhibit a U-shaped dose-response effect with an optimal dose of 1 microg/kg. The similarity between the effects of PLG and the synthetic peptidomimetics suggests a common mechanism of action. Finally, the synthetic peptidomimetics examined here, particularly peptidomimetic 5, were more effective than PLG in attenuating haloperidol-induced catalepsy.
Costain
W J
WJ
Department of Psychiatry and Behavioural Neuroscience, McMaster University, Hamilton, Ontario, Canada.
Buckley
A T
AT
Evans
M C
MC
Mishra
R K
RK
Johnson
R L
RL
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000009:adverse effects*; D009075:MSH Release-Inhibiting Hormone / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018716:Molecular Mimicry; D051381:Rats; D017207:Rats, Sprague-Dawley
D009075:MSH Release-Inhibiting Hormone; D006220:Haloperidol