Prenatal lead exposure enhances methamphetamine sensitization in rats☆

Abstract

Adult female rats were exposed to lead-free sodium acetate via gavage [0 mg (vehicle control)] or to 16 mg lead as lead acetate for 30 days prior to breeding. Following confirmation of breeding, the female animals continued to be exposed to their respective doses throughout gestation and lactation. When weaned, 16 control and 16 lead-exposed offspring were placed on regular water and food (leadexposure was discontinued) until postnatal day (PND) 70. At this time, one-half of the control animals and one-half of the lead-treatment animals received intraperitoneal (i.p.) injections of the vehicle (saline) for 10 successive days and the remaining animals in each exposure conditions received daily injections of 1.0 mg/kg (+)-methamphetamine (METH) for 10 days (N=8/group). Locomotion in automated chambers was monitored daily for 45 min post-injection. Subsequently, during dose-effect testing, all animals received consecutive daily i.p. injections of 0, 1.0, 2.0, and then 4.0 mg/kg METH. The results of the experiment showed that both control and lead-exposed animals exhibited heightened locomotor activity (i.e. behavioral sensitization) to the repeated administration of 1.0 mg/ kg METH. More importantly, animals developmentally (perinatally) exposed to lead showed more rapid sensitization than did their control counterparts. These data indicate that early lead exposure increases sensitivity to the locomotor-stimulating effects of METH. In contrast, identically exposed lead animals exhibit diminished METH dose-effect responding when tested in an intravenous (i.v.) self-administration paradigm (Rocha et al., 2008a;2008b).

Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

“…For methamphetamine, on the other hand, previous gestational and lactational exposure to lead resulted in reduced self-administration acquisition [43], self-administration at doses higher than non-exposed controls [41], and a decreased vulnerability to relapse [43] in adult animals. The motor stimulating effects of methamphetamine were enhanced in adult animals that had perinatal lead exposure, but the effects were only observed during early testing days with controls showing similar levels by later testing days [6]. …”

One-trial behavioral sensitization in preweanling rats: differential effects of cocaine, methamphetamine, methylphenidate, and d-amphetamine

“…On PD 21, the pretreatment groups were further subdivided and rats received a challenge injection of 1, 4, or 8 mg/kg (IP) methamphetamine prior to behavioral testing. Although adult rats and mice are typically challenged with a low to moderate dose of methamphetamine (1–4 mg/kg) on the test day (Suzuki et al 1997; Ago et al 2007; Clifford et al 2009), a broader dose range of methamphetamine was used in the present experiment to increase the likelihood of detecting a sensitized response.…”

In vivo distribution of lead in male and female rats after intraperitoneal and oral administration

“…Seven-week-old male rats weighing 150–180 g were used. The rats were divided into three major groups of males and females as follows: Group 1 served as control male and control female; group 2 males and females received 5 mg/kg body weight of lead intraperitoneally for 8 days while group 3 males and female rats was administered drinking water containing 100 ppm of lead acetate (Clifford et al, 2009; Miller et al, 2000; Sokol & Berman, 1991) for 18 days (following pre-experimental study of LD 50 ). Each group consisted of six rats.…”