Leading to Drug Abuse.
Nation and colleagues administered 8- and 16-milligram (mg) doses of lead by gavage to adult female rats starting 30 days before breeding them. Dosing continued through pregnancy and the birth and nursing of pups, ending at weaning. A control group received no lead. The 8-mg dose yielded a blood lead concentration in the mothers of some 20 micrograms per deciliter, comparable to the level often found in urban human populations.
At 30 and 90 dasts after birth, the researchers gave the pups cocaine doses of 1.25, 2.5, or 5.0 mg per kilogram of body weight. Unexposed rats responded to the drug at all doses, but rats whose mothers received the higher lead dose needed the highest cocaine dose to show a response. In the rats, the observed changes in sensitivity lasted more than a year--a period analogous to 20-30 years in humans, Nation says. And the neurologic effects lasted even after lead residues cleared the soft tissues, indicating that changes may be permanent. The pups' blood lead concentrations at the times of cocaine dosing were comparable to those common in urban children, who by socioeconomic circumstance may also be at greater risk of drug use.
Nation hypothesizes that lead may reduce production of the neuro-transmitter dopamine and thereby change sensitivity in exposed people, though he acknowledges that other mechanisms are possible. For one, lead may simply damage the central nervous system outright, explains Michael T. Bardo, director of graduate studies in psychology at the University of Kentucky in Lexington. The mechanism is readily testable by measuring dopamine release in the brain's "reward" center, or nucleus accumbens, while rats are performing a behavioral task, he says.
Nation observed a similar effect in previous studies of exposure to cadmium--prevalent in tobacco smoke--in unborn rats, though the mechanism of action is likely wholly different, since cadmium may not penetrate the blood-brain barrier. "If these contaminants are promoting drug use," Nation says, "then you have a relatively high public health risk."
But other researchers say the jury is still out on how--and whether--lead or other environmental agents may affect drug use. Although reasonably good evidence supports the notion that lowered dopamine concentrations may prompt an individual to use more of a drug to get high, other studies suggest that reduced dopamine concentrations may actually decrease the likelihood of drug abuse. Stephen M. Lasley, a neurotoxicologist at the University of Illinois College of Medicine at Peoria says it is just as likely that lead exposure may actually hamper a habit from forming because a first-time user may not experience a high. "It may take greater intake initially to establish a habit," he says.
The idea that lead is involved in drug use dates to morphine studies in the 1970s, according to Deborah Cory-Slechta, head of environmental medicine at the University of Rochester School of Medicine and Dentistry. Although she says "there's good evidence that the dopamine system is clearly targeted by lead," she says she'd like to see more proof, preferably drug self-administration studies--the gold standard of behavioral work--to be convinced there's a clear association with drug use. It's unlikely that exposure to lead would automatically lead to taking drugs because various sociocultural and psychologic factors are involved in the initiation of drug use, Bardo says. However, he adds, if exposure to lead increases the subsequent drug intake in an individual prone to substance abuse, then one would expect that the risk of dangers associated with overdose, such as heart attack and cocaine-induced psychosis, would be increased.
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|Publication:||Environmental Health Perspectives|
|Date:||Feb 1, 2001|
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