The effects of acrylamide treatment upon the dopamine receptor

Abstract

. (1981). Toxicol. Appl. Pharmacol. 58,[89][90][91][92][93][94][95][96][97][98][99]. 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 highaffinity 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 [ 3 H]spiroperidol binding at all acrylamide doses tested (50, 100, and 200 mJYkg 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 densicy 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. Twentyfour 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. Nonna! 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.

Protein malnourishment: A predisposing factor in acrylamide toxicity in pregnant rats

“…Acrylamide at a high dose is known to increase the activity of monoamine oxidase and decrease that of acetylcholinesterase in the developing rats and increase the striatal dopamine receptors in adult rats (Agrawal et al, 1981a(Agrawal et al, , 1981bHusain et al, 1987). Opposite effects as reflected by a decrease in the activity of monoamine oxidase and striatal dopamine receptors in our study may probably be due to nutritional influ-LPD LPD+ACR…”

The inhibition of cerebral high affinity receptor sites by lead and mercury compounds

“…In addition, regional distribution studies of receptor density confirmed the selective nature of binding. The stereospecificity of the spiroperidol binding was demonstrated using D and L butaclamol as competing agents (Agrawal et al 1980;Bondy 1980). The brain regions used for membrane preparation were chosen as containing a relatively high proportion of the receptor species being assayed (Table 1).…”

Biochemical changes in the brain consequent to dietary exposure of developing and mature rats to chlordecone (Kepone)

“…These changes were in the opposite direction to those caused by dosing of adult rats. A tendency of a toxic agent to cause opposite receptor changes in the brain of gestationally or neonatally exposed animals relative to adult exposure has also been observed in the case of acrylamide (Agrawal, et al .. 1981. Agrawal and Squibb, 1980).…”