Effects of ceftriaxone on ethanol drinking and GLT-1 expression in ethanol dependence and relapse drinking.

Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of alcohol (ethanol) in mice. Previous reports from our laboratory show that CIE increases extracellular glutamate in the nucleus accumbens (NAc) and that manipulating accumbal glutamate concentrations will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. A number of studies have shown that ceftriaxone increases GLT-1 expression, the major glutamate transporter, and that treatment with this antibiotic reduces ethanol drinking.

Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport.

Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point.

Increased extracellular glutamate in the nucleus accumbens promotes excessive ethanol drinking in ethanol dependent mice.

Using a well-established model of ethanol dependence and relapse, this study examined adaptations in glutamatergic transmission in the nucleus accumbens (NAc) and their role in regulating voluntary ethanol drinking. Mice were first trained to drink ethanol in a free-choice, limited access (2 h/day) paradigm. One group (EtOH mice) received repeated weekly cycles of chronic intermittent ethanol (CIE) exposure with intervening weeks of test drinking sessions, whereas the remaining mice (CTL mice) were similarly treated but did not receive CIE treatment.

Effect of operant self-administration of 10% ethanol plus 10% sucrose on dopamine and ethanol concentrations in the nucleus accumbens.

Although operant ethanol self-administration can increase accumbal dopamine activity, the relationship between dopamine and ethanol levels during consumption remains unclear. We trained Long-Evans rats to self-administer escalating concentrations of ethanol (with 10% sucrose) over 7 days, during which two to four lever presses resulted in 20 min of access to the solution with no further response requirements. Accumbal microdialysis was performed in rats self-administering 10% ethanol (plus 10% sucrose) or 10% sucrose alone.