Developmental Lead Exposure Alters the Stimulatory Properties of Cocaine at PND 30 and PND 90 in the Rat

Abstract

The aim of this study was to examine the effects of perinatal lead exposure on locomotor responding following acute and repeated cocaine challenges (sensitization).Lead poisoning continues to present major health concerns nationwide, and this situation is especially problematic among children. Recent sociodemographic data indicate the threat of lead toxicity is especially great among economically disadvantaged, nonwhite, and inner-city children (Goldman and Carra 1994;Pirkle et al. 1994). Along these lines, a 1999 report alarmingly places the "at risk" figure for children suffering from excessive lead exposure at around 70% in major metropolitan areas of the United States (cf., Mielke 1999).The sizable literature on developmental lead poisoning understandably has focused on global disturbances produced by early contaminant exposure that may have an enduring impact on the quality of life. In this sense, the data are compelling with respect to showing that even low-level lead exposure during development can occasion long-lasting neurobehavioral disturbances that compromise adult adaptive abilities and threaten stability. In this regard, functional deficits in cognitive and intellectual processing have been shown to persist well into the adult cycle of humans, rodents, and nonhuman primates (e.g., Bellinger et al. 1987). In addition, it seems that even emotional expression and attendant psychosocial phenomena may be influenced by lead ex- N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 4 Developmental Lead Exposure and Cocaine 445 posure during early development (Needleman et al. 1996).In the present report, our objective was to investigate interactive relations between developmental lead exposure and drug sensitivity later in the life cycle. This is an especially pertinent issue given that lead uniquely threatens sub-populations where drug abuse is more common, i.e., urban minorities . Clearly, experiential elements, availability, drug history, poverty, etc., must be considered in the list of dispositional factors that determine drug habits in humans. But it also must be considered that other types of environmental events may contribute to the abuse potential of selective drugs. That is, to the extent that lead or any other xenobiotic chemical alters the impact of a set delivery of a drug, motivational features related to drug seeking and taking may be redefined and therein influence maintenance responding and/or the effectiveness of certain pharmacotherapies for drug abuse (Mello et al. 1995).The development of behavioral sensitization during repeated administration of psychomotor stimulants is a well-characterized phenomenon which has received considerable attention because of its proposed relevance to drug addiction (Robinson and Berridge 1993;Wise and Bozarth 1987;Wolf et al. 1995) and psychosis (Post et al. 1992;Segal and Schuckit 1983). Therefore, the procedure was employed here in an effort to determine the effects of lead exposure during lactation and gestation on cocaine-induced changes in locomotor re...

Cocaine self-administration in male and female rats perinatally exposed to PCBs: Evaluating drug use in an animal model of environmental contaminant exposure.

“…Likewise, other studies using animal models have reported that developmental exposure to lead (Clifford et al, 2011; D. K. Miller, Nation, & Bratton, 2000, 2001; Nation, Miller, & Bratton, 2000), cadmium (Nation & Miller, 1999), manganese (Guilarte et al, 2008; McDougall et al, 2008; Reichel et al, 2006), and methylmercury (Eccles & Annau, 1982; Newland, Reed, & Rasmussen, 2015; Rasmussen & Newland, 2001; Reed et al, 2008; Wagner, Reuhl, Ming, & Halladay, 2007) alter dopamine neurotransmission and alter the response to experimenter -administered psychostimulants during adulthood, often in a sex-specific manner. This is the first study to demonstrate that rats perinatally exposed to PCBs exhibit differences in the propensity to acquire self -administration of cocaine and is one of a handful of other studies demonstrating monoamine-disrupting environmental contaminants such as lead (Nation, Cardon, Heard, Valles, & Bratton, 2003; Nation, Smith, & Bratton, 2004; Rocha, Valles, Bratton, & Nation, 2008; Rocha, Valles, Cardon, Bratton, & Nation, 2005; Rocha, Valles, Hart, Bratton, & Nation, 2008; Valles, Rocha, Cardon, Bratton, & Nation, 2005) and cadmium (Cardon, Rocha, Valles, Bratton, & Nation, 2004) can also alter psychostimulant self-administration in adulthood after perinatal exposure.…”

Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat

“…This procedure has been used in previous developmental lead studies to ensure stable blood/tissue levels (cf. Nation et al, 2000;2003;Rocha et al, 2004). The present lead concentration was selected based on previous studies that found it produces differential behavioral effects while not altering dam body weights or the locomotor ability of pups (see Miller et al, 2000).…”

Developmental lead exposure alters methamphetamine self-administration in the male rat: Acquisition and reinstatement

“…This procedure has been used in our previous developmental lead studies to ensure stable blood/tissue levels (cf. Miller et al, 2000;Nation et al, 2000Nation et al, , 2003Rocha et al, 2004;Valles et al, 2005). The present lead concentration was selected based on previous investigations that found it produces differential behavioral effects while not altering dam weights or the locomotor ability of pups .…”

“…Procedures-Surgery was performed on test offspring at PND 60, which is a point demonstrated to be within the adult timeframe of behavioral change produced by developmental lead exposure (Miller et al, , 2001Nation et al, 2000Nation et al, , 2003. Using a backplate surgical procedure, implantation of chronic indwelling jugular catheters was performed using sterile techniques as described in detail elsewhere (Nation et al, 2003).…”