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

Abstract

The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16-mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-hr autoshaping period preceded a 3-hr selfadministration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/ kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on a FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16-mg lead throughout gestation and lactation when a 0.02 mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.

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

“…Rocha et al (2008) found that rats exposed developmentally to the identical lead treatment employed here were slower to acquire self-administration responding for a .02 mg/kg methamphetamine infusion than their control counterparts. Moreover, similarly exposed animals were less likely than controls to reinstate responding in an extinction context when administered a drug (methamphetamine [i.p.])…”

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

“…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. Thus, there is converging research to demonstrate that exposure to monoamine-disrupting chemicals during early development can promote drug-seeking later in life.…”

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

“…In adult animals, previous gestational and lactational exposure to lead produced an increase in the sensitivity to cocaine as exhibited by faster acquisition of self-administration behavior [42], maintenance of self-administration at doses lower than non-exposed controls [32], a higher vulnerability to relapse [30], and an increase in the motor stimulating effects [31]. 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].…”