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-h autoshaping period preceded a 3-h self-administration 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 an 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.

Figure 1

Cumulative percentage (%) of Group 0-mg (n= 7) and Group 16-mg (n=8) rats meeting the criterion for the acquisition of methamphetamine (0.02 mg/kg) self-administration within the 35-day limit. Open symbols and closed symbols represent Group 0-mg and Group 16-mg conditions, respectively (Experiment 1).

Figure 2

Mean (SEM) number of active (right) lever responses for Groups 0-mg (n=9) and 16-mg (n=7) during hrs 1–4 at each priming dose of reinstatement. Methamphetamine (0.04 mg/kg/inf) was available during hr 1 and saline infusions were delivered during hrs 2–4 (Experiment 2). Note that the values on the horizontal axis refer to the assignments of the methamphetamine priming dose to be received by each group during reinstatement testing (hr 5)

Figure 3

The mean percent of baseline (hr 1 methamphetamine [i.v.]) responding for Groups 0-mg (n=9) and 16-mg (n=7) during hr 5 (reinstatement testing) following different priming doses of methamphetamine (i.p.). The symbol * above the bar indicates that Group 16-mg administered more saline infusions (made more responses on the active lever) following the prime than their control counterparts (Group 0-mg); p<.05 (Experiment 2).