Previous investigations have shown that recurrent exposure to dietary lead or cadmium results in an attenuated response to ip injections of cocaine HCL. Specifically, these metals reduced the psychostimulant effects of a 10mg/kg dose of cocaine HCL, but not a 20 or 40 mg/kg dose, in adult male rats. Because lead and cadmium are competitive with calcium, and inasmuch as calcium-mediation is central to the neurochemical and behavioral effects of cocaine, it is possible that these toxicants may attenuate the pharmacologic effects of cocaine. Relevant to this issue, four separate lines of investigation are proposed. Experiments 1 and 2 will examine the effects of chronic low- level exposure to lead or cadmium on the rate-dependent effects of acute cocaine exposure, in an operant context. The second series of experiments will assess the impact of lead (Exp. 3) or cadmium (Exp. 4) on the discriminative stimulus effects associated with cocaine. Experiments 5 and 6 will test for the rewarding effects of cocaine in lead-treated and cadmium-treated animals, using an intravenous self- administration paradigm. Also, the effects of lead (Exp. 7) or cadmium (Exp. 8) on cocaine-induced increases in extracellular levels of dopamine within the nucleus accumbens and prefrontal cortex will be determined, using a microdialysis technique. Finally, the effect of lead or cadmium on cocaine pharmacokinetics will be assessed (Exp. 9-10). In all experiments a full range of drug doses will be used. The results from this project will provide valuable information about the possible link between xenobiotic contamination and the response to a prominently abused psychoactive drug.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
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Drug Abuse Biomedical Research Review Committee (DABR)
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Texas A&M University
Schools of Arts and Sciences
College Station
United States
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Smith, Kelly R; Nation, Jack R; Bratton, Gerald R (2002) The effects of developmental cadmium exposure on morphine sensitization and challenge with selective D(1) and D(2) antagonists. Pharmacol Biochem Behav 72:581-90
Miller, D K; Nation, J R; Bratton, G R (2001) The effects of perinatal exposure to lead on the discriminative stimulus properties of cocaine and related drugs in rats. Psychopharmacology (Berl) 158:165-74
Miller, D K; Nation, J R; Bratton, G R (2000) Perinatal exposure to lead attenuates the conditioned reinforcing properties of cocaine in male rats. Pharmacol Biochem Behav 67:111-9
Nation, J R; Miller, D K; Bratton, G R (2000) Developmental lead exposure alters the stimulatory properties of cocaine at PND 30 and PND 90 in the rat. Neuropsychopharmacology 23:444-54
Nation, J R; Miller, D K; Bratton, G R (2000) Dietary cadmium exposure alters characteristics of training, substitution, and tolerance when morphine is used as a discriminative stimulus. Neurotoxicology 21:553-67
Miller, D K; Nation, J R; Jost, T E et al. (2000) Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats. Pharmacol Biochem Behav 67:281-90
Nation, J R; Miller, D K (1999) The effects of cadmium contamination on the discriminative stimulus properties of cocaine and related drugs. Exp Clin Psychopharmacol 7:90-102
Miller, D K; Palme, K M; Najvar, S A et al. (1999) Chronic cadmium exposure attenuates conditioned place preference produced by cocaine and other drugs. Pharmacol Biochem Behav 64:15-20
Nation, J R; Wellman, P J; Livermore, C L et al. (1997) Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium-exposed rats following acute or chronic intraperitoneal administration of cocaine. Toxicol Lett 92:47-57
Nation, J R; Miller, D K; Livermore, C L (1997) Chronic exposure to cadmium attenuates behavioral sensitization to morphine. Psychopharmacology (Berl) 131:248-54

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