Methamphetamine self-administration in rats developmentally exposed to lead

Abstract

Methamphetamine is gaining mainstream popularity across the United States at the same time that lead exposure remains at elevated levels. Perinatal (gestation/lactation) lead exposure has been found to modify the reward efficacy of various drugs of abuse (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse. Lead-induced changes in sensitivity to methamphetamine have not been examined in animals perinatally exposed to lead. Accordingly, four studies were conducted to examine the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across all relevant transition points of drug addiction. Adult female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 60 and PND 90) and subsequently were randomly assigned to one of the four studies mentioned above, using only one male rat per litter for each study. In Experiment 1, an acquisition study revealed that perinatal exposure to environmentally relevant levels of lead resulted in a smaller percentage of rats reaching the criterion for intravenous (i.v.) methamphetamine (.02 mg/kg) acquisition, relative to non-exposed controls. In Experiment 2, a dose-effect curve yielded a biphasic pattern of attenuation of the self-administration of methamphetamine (.04 mg/kg) in lead-exposed animals. In Experiment 3, lead-exposed animals reached lower breaking points for methamphetamine (.04 mg/kg) in a progressive ratio task, in comparison to control animals. Finally in Experiment 4, a reinstatement study revealed that perinatally leadexposed animals showed a decreased propensity to relapse to methamphetamine (.04 mg/kg) self-administration after a period of forced abstinence. The general attenuation to the rewarding efficacy of methamphetamine observed in animals perinatally exposed to lead may functionally translate into a form of tolerance or counteradaptation. The data collected from these four studies further strengthen the possibility that pollutants in the environment may play a modulatory role in substance abuse.