Browsing by Author "Rocha, Angelica"
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Item Acquisition of cocaine and heroin self-administration in rats developmentally exposed to lead(Texas A&M University, 2005-08-29) Rocha, AngelicaRationale: The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing vulnerability to initiate drug use. Objectives: The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) heroin self-administration and cocaine self-administration using an automated procedure that included both Pavlovian and operant components. Methods: For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration 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 and subsequently were tested daily in a preparation where sessions included an initial 3-hr autoshaping period followed by a 3- hr self-administration period. During autoshaping, heroin (.018 mg/kg) infusions were paired with the extension and retraction of a lever when a lever press was not made for 15 sec, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 10 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. Results: Findings from Experiment 1 showed the proportion of rats meeting the lever-press response criterion for heroin when tested as adults was lower among lead-exposed animals. In Experiment 2, cocaine (.20 mg/kg) was presented to animals that underwent the same metal-exposure regimen, surgical procedures and methods with variations only in the number of infusions that were automatically administered during the Pavlovian component. Criterion for cocaine acquisition was a mean of 50 infusions over a two-day. In Experiment 2, a greater proportion of leadexposed animals reached the criterion for cocaine acquisition. Conclusions: Developmentally lead-exposed animals showed a decrease in vulnerability to initiate drug-taking behavior when presented with heroin in the adult phase, relative to controls. In contrast, developmentally lead-exposed animals showed an enhanced vulnerability to reach the criterion for cocaine self-administration. Clinical relevance of developmental exposure to lead and the attendant vulnerability to self-administer drugs of abuse is discussed.Item Methamphetamine self-administration in rats developmentally exposed to lead(2009-05-15) Rocha, AngelicaMethamphetamine 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.