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.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-1370 |
| Date | 15 May 2009 |
| Creators | Rocha, Angelica |
| Contributors | Nation, Jack, Wellman, Paul |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Dissertation, text |
| Format | electronic, application/pdf, born digital |
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