Elsevier

Biological Psychiatry

Volume 63, Issue 2, 15 January 2008, Pages 214-221
Biological Psychiatry

Original Article
Prenatal Exposure to Cocaine Increases the Rewarding Potency of Cocaine and Selective Dopaminergic Agonists in Adult Mice

https://doi.org/10.1016/j.biopsych.2007.01.014Get rights and content

Background

Substance abuse during pregnancy results in persistent affective and behavioral deficits in drug-exposed children, and increased rates of substance abuse have been observed in young adults prenatally exposed to drugs of abuse. Animal models of prenatal cocaine exposure have yielded differing results depending on the behavioral method used to assess drug potency.

Methods

The effects of cocaine, the dopamine D1 agonists SKF-81297 and SKF-82958, and the D2 agonist quinpirole on intracranial self-stimulation were measured in adult Swiss-Webster mice exposed to cocaine in utero (40 mg/kg/day) and vehicle controls with the curve-shift method of brain stimulation-reward (BSR) threshold determination.

Results

The reward-potentiating effects of cocaine (0.3–30 mg/kg IP) and SKF-82958 but not SKF-81297 on BSR were increased in adult male but not female mice after prenatal cocaine exposure. Quinpirole exerted biphasic effects on BSR, both elevating (0.1–0.3 mg/kg IP) and lowering (1.0–10 mg/kg IP) reward thresholds. Both effects of quinpirole were also enhanced in adult male mice after prenatal cocaine exposure.

Conclusions

Prenatal cocaine exposure results in increased reward-potentiating potency of cocaine on BSR in adult mice in a sexually-dimorphic manner. This augmented rewarding effect of cocaine is also associated with increased sensitivity to both D1- and D2-selective agonists.

Section snippets

Animal Care and Handling

All animal procedures were carried out according to the National Institutes of Health Guide to the Care and Use of Laboratory Animals and were approved by the Subcommittee on Research Animal Care at Massachusetts General Hospital.

In Utero Cocaine Exposure

Mice were exposed to cocaine in utero as previously described (27). Adult timed-pregnant white Swiss-Webster dams (Taconic Labs, Germantown, New York) were allowed access to food and water ad libitum and housed on a 12-hour (7:00 am light–7:00 pm dark) cycle. Two

Results

The ICSS electrode tip positions are shown in Figure 1. No significant effects of gender [F(1,44) = .05, p = .82] or prenatal treatment [F(1,44) = .11, p = .75] were observed on baseline BSR thresholds (θ0), determined as the total charge delivery in Coulombs (μA × μsec) at the stabilized baseline threshold before saline determinations (Table 1), indicating that prenatal cocaine exposure does not alter responding for BSR and that ICSS does not differ between males and females.

The effects of

Discussion

Most preclinical investigations of consequences of prenatal exposure to drugs of abuse have employed passive behavioral methods, particularly open-field exploration or locomotor behavior. The relatively fewer studies examining appetitive behavior with either instrumental or classical conditioning methods have shown subtle but reproducible and consistent effects of gestational exposure to drugs of abuse (reviewed in 14). Most investigations of operant behavior after such exposures have

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