Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model

Abstract

A new surgical preparation is described with which it is possible to quantify the degree of supersensitivity to dopamine receptor-stimulating agents using the rotational model. One group of rats received a unilateral injection of 6-hydroxydopamine which destroys the dopamine-containing neurons in one hemisphere, followed by a diencephalic electrocoagulation which interrupts both afferents and efferents of the striato-pallidal complex in the opposite hemisphere. Another series of animals received only the unilateral electrocoagulation. When given appomorphine both groups of animals rotated toward the side of the electrocoagulation. However, the 6-hdroxydopamine-treated animals were 10-40 times more sensitive to the behavioral effect of the drug. These results contrast with previous reports in which behavioral sensitivity to apomorphine was increased 2- to 7-fold following partial degeneration of central dopamine neurons of following the chronic adminstration of dopamine synthesis inhibitors of receptor blocking agents. The extent of loss of dopamine appears to be a critical factor in determining the degree of supersensitivity which will develop.