Effect of cyclo(Leu-Gly) on reserpine-induced hypomotility and increases in cortical β-adrenergic receptors

Previous studies have indicated that the endogenous peptide, melanotropin release inhibiting factor (MIF) and its analog cyclo(Leu-Gly) (CLG) facilitate dopamine (DA) receptor agonist binding and inhibit DA receptor supersensitivity induced by neuroleptics and opiates. The effect of CLG was tested on β-adrenergic hypersensitivity induced by reserpine to ascertain whether CLG has effects on other neuronal systems besides DA. Administration of reserpine to rats induced hypomotility and enhanced binding of [³H]dihydroalprenolol (DHA) to cortical membranes. Concurrent administration of CLG blocked both the hypomotility and the enhanced [³H]DHA binding to cortical membranes. Lithium has also been shown to prevent reserpine induced hypomotility and increased cortical [³H]DHA binding. These studies suggest that CLG may be producing its effect either like lithium or by an amphetamine like action. If CLG can be shown to have lithium like activity, it could prove to be useful in the treatment of mania.