The effects of acrylamide treatment upon the dopamine receptor

Abstract

The binding of tritiated spiroperidol to striatal membranes prepared from acrylamide-treated male 6-week-old rats and matched controls has been studied. This binding has high-affinity characteristics and is stereospecific and reversible. Equilibrium was attained within 15 min at 37°C. The extent of binding was much more pronounced in the striatum than in any other brain region and was not detectable within the cerebellum or spinal cord. Regional distribution of binding and competition studies with other pharmacologic agents suggested a correspondence between the location of ligand-membrane complex formation and the dopamine receptor. Twenty-four hours after a single oral administration of acrylamide there was a significant increase in [ 3H]spiroperidol binding at all acrylamide doses tested (50, 100, and 200 mg/kg body weight). However, there was no significant change in striatal dopamine levels of treated animals. Kinetic analysis of animals treated with 100 mg acrylamide/kg suggested increased affinity of receptors of treated animals toward the labeled ligand. Receptor density was only slightly elevated in experimental animals. Effects were also studied in rats that had received 10, 20, or 30 mg/kg acrylamide daily for 10 days. Twenty-four hours after the last dose there was a major increase in spiroperidol binding in treated animals. Scatchard plot analysis again revealed that this change was largely attributable to a change in the dissociation constant of the binding interaction but also there was an increase in the overall number of receptor sites. Normal values were restored within 8 days after cessation of dosing. This illustrates that, under the conditions of this experiment, the effect of acrylamide on a central neurotransmitter system is reversible.