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For several years, our laboratory has investigated the role for the HPA axis in cocaine reinforcement. Two classes of drugs that we have studied include corticosterone synthesis inhibitors (e.g., metyrapone) and benzodiazepine receptor agonists (e.g., oxazepam). In the experiments described in this manuscript, we tested the effects of various doses of(More)
The effects of cocaine on defensive withdrawal behavior in rats and elevated plus-maze behavior in mice were investigated. Cocaine (20 mg/kg IP) injected daily for 7 or 14 days induced defensive withdrawal; that is, the latency to emerge from a small chamber in an open field and the mean time in the chamber were both significantly increased. Acute cocaine(More)
RATIONALE We have previously reported that pretreatment with benzodiazepines reduces intravenous cocaine self-administration in rats. OBJECTIVE This experiment was designed to investigate whether or not benzodiazepines would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer. MATERIALS AND METHODS(More)
Although our lab, as well as several others, has demonstrated a role for corticosterone in cocaine self-administration, there are no studies of the central dynamics of this hormone over the course of a behavioral session when rats are self-administering cocaine or receiving passive injections. The assay of corticosterone in microdialysates collected during(More)
BACKGROUND We have previously reported that combining low doses of oxazepam and metyrapone (OX/MET) reduces intravenous cocaine self-administration without affecting stress-hormone levels. We hypothesized that the combination of OX/MET would also inhibit the reinstatement of cocaine or methamphetamine seeking induced by the presentation of a conditioned(More)
Several compounds that potentiate GABA-induced inhibitory currents also decrease stress, anxiety and addiction-related behaviors. Because of the well-established connection between stress and addiction, compounds that reduce stress-induced responses might be efficacious in treating addiction. Since endogenous neurosteroids such as allopregnanolone may(More)
Although cocaine dependence affects an estimated 1.6 million people in the USA, there are currently no medications approved for the treatment of this disorder. Experiments performed in animal models have demonstrated that inhibitors of the stress response effectively reduce intravenous cocaine self-administration. This exploratory, double-blind,(More)
Investigation of the role of stress in cocaine addiction has yielded an efficacious combination of metyrapone and oxazepam, hypothesized to decrease relapse to cocaine use by reducing stress-induced craving. However, recent data suggest an extra-adrenal role for metyrapone in mediating stress- and addiction-related behaviors. The interactions between the(More)
Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying(More)
RATIONALE Methamphetamine (MA) increases extracellular dopamine (DA) and at chronic high doses induces toxicity as indicated by decreased expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Notably, rats will self-administer MA in escalating quantities producing such toxicity. However, the impact of MA at sub-toxic doses on DA regulation(More)