Developmental exposure to cadmium alters responsiveness to cocaine in the rat

• Published in: Drug and alcohol dependence Vol. 72; no. 1; pp. 1 - 11
• Main Authors: Smith, Kelly R, Nation, Jack R
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 24-10-2003; Elsevier Science
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Cadmium; Cadmium - adverse effects; Cadmium - analysis; Cerebral Cortex - chemistry; Cocaine; Cocaine - administration & dosage; Cocaine - metabolism; Conditioned place preference; Drug addictions; Embryo, Mammalian - drug effects; Female; Injections, Intravenous; Kidney - chemistry; Liver - chemistry; Locomotion - drug effects; Medical sciences; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sensitization; Toxicology; Cadmium; Cocaine; Sensitization; Conditioned place preference; Statistical analysis; Rat; Rodentia; Perinatal; Exploration; Exposure; Experimental study; Response; Ester; Vertebrata; Mammalia; Animal; Comparative study
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(03)00170-4

The purpose of the present report was to investigate the potential interactive relation between perinatal (gestation/lactation) cadmium exposure and changes in responsiveness to cocaine. In Experiment 1, adult female rats were exposed to a diet containing 50 ppm cadmium (as cadmium chloride) or a diet containing no added cadmium for 30 days prior to breeding with nonexposed males. The metal-exposure regimen continued throughout gestation, and for 15 days of lactation, at which time all animals were placed on standard rat chow diets containing no added cadmium for the remainder of the investigation. Atomic absorption assays confirmed that cadmium concentrations were significantly elevated in metal-exposed dams, littermates, and test animals. Offspring were weaned on postnatal day (PND) 21 and commenced cocaine sensitization testing on PND 70. Testing operations for controls and animals perinatally exposed to cadmium consisted of 21 daily i.p. injections of vehicle (saline) or 10 mg/kg cocaine HCl, and subsequent recording of locomotor activity. Subsequently, across successive days, all animals received 0, 10, and 20 mg/kg cocaine challenges. The results showed that cocaine sensitization was attenuated in animals perinatally exposed to cadmium. A similar pattern of antagonism was observed in Experiment 2 where a higher dose of cocaine was required to produce conditioned place preference (CPP) in cadmium-exposed animals. The implications of these findings with respect to the interactive role of cadmium in the dynamics of cocaine use/abuse remain unclear.