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Increased vulnerability to self-administer cocaine in mice prenatally exposed to cocaine
Beatriz A Rocha1, Andy N Mead, Barry E Kosofsky
1Behavioral Neuroscience Branch, National Institute of Drug Abuse--Intramureal Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. beatriz_rocha@merck.com
Insights
Prenatal cocaine exposure in mice increases the likelihood of acquiring cocaine self-administration in adulthood. This study demonstrates a link between prenatal cocaine exposure and heightened vulnerability to cocaine-taking behavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- An estimated 40,000 infants annually in the U.S. are exposed to crack cocaine prenatally.
- Prenatal cocaine exposure may increase vulnerability to cocaine addiction in offspring.
Purpose of the Study:
- To test if prenatal cocaine exposure significantly increases subsequent cocaine-taking behavior in mice.
- To investigate the dose-dependent effects of prenatal cocaine exposure on adult cocaine self-administration.
Main Methods:
- Swiss Webster male mice were exposed to cocaine (40 mg/kg or 20 mg/kg) or saline during gestation.
- Adult mice underwent cocaine self-administration testing using intravenous catheters.
- Cocaine doses ranged from 0.25 to 2.0 mg/kg per injection under a fixed ratio 1 schedule.
Main Results:
- Acquisition of food-reinforced responding and cocaine self-administration was dose-dependent.
- Mice prenatally exposed to higher doses of cocaine (40 mg/kg) were more likely to acquire cocaine self-administration at moderate doses (1.0-2.0 mg/kg).
- Logistic regression confirmed a positive correlation between prenatal cocaine exposure and the likelihood of acquiring cocaine self-administration.
Conclusions:
- Prenatal exposure to higher doses of cocaine increases the probability of acquiring cocaine self-administration in adulthood.
- These findings provide evidence for modulated vulnerability to cocaine-taking behavior following prenatal cocaine exposure.
- The study highlights potential long-term neurobehavioral consequences of prenatal drug exposure.
Rationale:
At least 40,000 infants born each year in the U.S. are estimated to have been exposed to crack cocaine and, therefore, may be at risk for increased vulnerability to cocaine addiction.
Objectives:
The present study tested the hypothesis that prenatal exposure to cocaine significantly increased subsequent cocaine-taking behavior in mice.
Methods:
Swiss Webster male mice that had been exposed to cocaine in utero were tested at 5 months of age in the cocaine self-administration paradigm. They were the offspring of dams that received one of the following treatments during gestation days 8-17: cocaine (40 mg/kg or 20 mg/kg per day; COC40 and COC20 mice, respectively), saline with access to food ad libitum (SAL mice), or saline with access to food restricted to that of the COC40 dams (i.e., pair-fed; SPF40 mice). Mice were initially trained to lever press for a condensed-milk solution, were implanted with an indwelling intravenous (i.v.) catheter and, subsequently, allowed to self-administer cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg per injection) under a fixed ratio (FR) 1 schedule of reinforcement.
Results:
Latency for acquisition of food-reinforced responding appeared to be independent of prenatal treatment, as was acquisition of cocaine self-administration, which was found to be dose dependent. Both COC40 and SAL mice reached cocaine self-administration criteria at 1.0 mg/kg or 2.0 mg/kg per injection doses, while neither group did so at lower doses. It was also observed that, at each of the doses tested, a higher number of COC40 mice reached criteria for acquisition. A logistic regression analysis confirmed that the likelihood for acquiring cocaine self-administration was positively correlated to prenatal exposure to cocaine and the dose of cocaine tested.
Conclusions:
These data provide evidence, for the first time, that prenatal exposure to higher doses of cocaine increase the probability of acquiring cocaine self-administration at moderate doses during adulthood and modulate vulnerability to cocaine-taking behavior in mice.