title: Brain and plasma levels of cocaine and benzoylecgonine in lead-expose and cadmium-exposed rats following acute or chronic intraperitoneal administration of cocaine.
abstract: Previous investigations of metal/cocaine interactions have shown that chronic oral exposure to inorganic lead or cadmium attenuates the psychoactive effects of acute or repeated administration of cocaine. The purpose of this investigation was to assess the possibility that such interactive effects may derive from metal-induced disturbances in cocaine pharmacokinetics, i.e., delivery of cocaine to critical biologic sites may be disrupted by metal contamination. In this study, adult male rats were exposed to purified diets containing 250 ppm lead acetate (Group Lead), 100 ppm cadmium chloride (Group Cadmium), or unadulterated laboratory chow (Group Control); n = 48/exposure condition. Following ad libitum access to their respective diets in the home cage for 45 days, half the animals from each exposure regimen received single daily IP injections of 5, 10, or 20 mg/kg cocaine HCl for a period of 7 days (n = 8/group). The remaining half the animals received repeated daily injections of saline during this pretreatment phase. On the day following pretreatment, animals previously receiving cocaine injections were administered a single cocaine test challenge at a dose equal to that received in pretreatment. Similarly, saline pretreatment animals received either 5, 10, or 20 mg/kg cocaine. The results of this investigation did not reveal reliable evidence of metal-related differences in brain levels of cocaine. Plasma cocaine and benzoylecgonine (BE) levels also were essentially the same for control and metal-exposed animals. The failure to show that lead or cadmium alters the disposition of cocaine in brain or plasma underscores the need to pursue alternative accounts of metal/cocaine interactions.
authors.affiliation: Department of Psychology, Texas A & M University, College Station 77843, USA. jrn@psyc.tamu.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Nation
authors.forename: P J
authors.initials: PJ
authors.lastname: Wellman
authors.forename: C L
authors.initials: CL
authors.lastname: Livermore
authors.forename: D K
authors.initials: DK
authors.lastname: Miller
authors.forename: G R
authors.initials: GR
authors.lastname: Bratton
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019256:Cadmium Chloride / Q000097:blood / Q000633:toxicity*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000097:blood*; D009714:Nucleus Accumbens / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009294:Narcotics; D009942:Organometallic Compounds; C005618:benzoylecgonine; D003042:Cocaine; D019256:Cadmium Chloride; C008261:lead acetate