Chronic Developmental Lead Exposure increases μ-Opiate Receptor Levels in the Adolescent Rat Brain

Abstract

Opioid use and abuse has reached epidemic proportion in the United States resulting in a significant numbers of deaths due to overdose. While environmental factors are implicated in opioid addiction, less is known about the role of exposure to environmental pollutants on the brain opioid system. Human and preclinical studies have suggested an association between childhood lead (Pb2+) intoxication and proclivity to substance abuse and delinquent behavior. Opioid receptors are involved in the biological effects of opioids and other drugs of abuse. In this study, we examine the effect of chronic developmental Pb2+ exposure on -opioid receptor (MOR) levels in the rat brain using [3H]-D-Ala2-MePhe4-Gly-ol5 enkephalin ([3H]-DAMGO) quantitative receptor autoradiography. Our results indicate that chronic developmental Pb2+ exposure increases the levels of [3H]-DAMGO specific binding to MOR in several limbic regions of the brain in male and female rats during the pre-adolescence (PN14) and early-adolescence (PN28) period. These changes were less pronounced in late-adolescence (PN50) and adult (PN120) animals. Our findings are important because the pre-adolescence and early adolescence period is a time in which there is higher engagement in reward and drug seeking behaviors in humans. In summary, we show that chronic exposure to Pb2+ an ubiquitous and well-known environmental contaminant and neurotoxicant, alters MOR levels in brain regions associated with addiction circuits in the adolescent period with important implications to opioid drug use and abuse.