Enhanced Acquisition of Cocaine Self-Administration in Rats Developmentally Exposed to Lead

Abstract

The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing the vulnerability to use drugs. The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous cocaine self-administration using an automated procedure that included both Pavlovian and operant components. For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day (PND) 21). Animals born to control or lead-exposed dams subsequently were tested daily as adults in a preparation where sessions included an initial 3-h autoshaping period followed by a 3-h self-administration period where 0.20 mg/kg cocaine was delivered contingently. During autoshaping, intravenous cocaine infusions were paired with the extension and retraction of a lever, while infusions occurred during selfadministration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 50 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. In Experiment 1, accelerated rates of acquisition of cocaine self-administration were evident for lead-exposed animals relative to controls. Overall, the number of selfadministered cocaine infusions per session was significantly higher for lead-exposed rats as compared to control rats. Experiment 2 replicated Experiment 1 except that a higher dose of cocaine (0.80 mg/kg) was employed as the reinforcer, and 30 infusions/session was the set criterion. At the higher cocaine dose (Experiment 2), acquisition rates for control and lead-exposed animals were not markedly different, and significantly different infusion rates were not observed.

Impairment of acquisition of cocaine self-administration in rats maintained on a high-fat diet

“…Using a backplate technique, implantation of chronic indwelling jugular catheters was performed using sterile techniques as described in detail elsewhere (Nation et al, 2003;Rocha et al, 2005). The rats were allowed 5 days to recover from surgery before commencing cocaine self-administration testing.…”

“…The cocaine dose (0.20 mg/kg) was chosen based on data from previous studies that show this dose is marginally reinforcing, and does not produce satiation or motoric impairments (Campbell and Carroll, 2001;Rocha et al, 2005).…”

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

“…It has been argued that the rate of acquisition of drug selfadministration may serve as a predictor of later drug-taking behavior, possibly influencing the transition from drug use to addiction (refer to Rocha et al, 2005). Accordingly, in Experiment 1 an acquisition paradigm developed by Carroll and associates (Campbell and Carroll, 2001;Carroll and Lac, 1997) was employed to train lead-exposed and control animals to press a lever for a methamphetamine-reinforcement in a consistent manner, with minimal intrusions.…”

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

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AbstractPerinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse (Nation et al, 2003;Rocha et al, 2005). However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead.

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“…For instance, perinatal lead exposure has been shown to enhance the rate of acquisition of the self-administration of cocaine (Rocha et al, 2005), produce a shift to the left in the dose effect curve , and increase vulnerability to reinstatement (Nation et al, 2003). By contrast, developmental lead exposure attenuates the psychoactive effects of heroin (Rocha et al, 2004).…”