Modulatory effects of PLG and its peptidomimetics on haloperidol-induced catalepsy in rats

Abstract

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 (Cα, α-dialkylated glycyl residues with lactam bridge constraint [ 1–4] and without [ 5–8]) were tested in the same manner (at a dose of 1 μg/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 μg/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.