Glycogen synthase kinase 3 beta regulates ethanol consumption and is a risk factor for alcohol dependence.

Understanding how ethanol actions on brain signal transduction and gene expression lead to excessive consumption and addiction could identify new treatments for alcohol dependence. We previously identified glycogen synthase kinase 3-beta (Gsk3b) as a member of a highly ethanol-responsive gene network in mouse medial prefrontal cortex (mPFC). Gsk3b has been implicated in dendritic function, synaptic plasticity and behavioral responses to other drugs of abuse.

Translating Alcohol Research: Opportunities and Challenges.

Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient.

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use.

Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity.

The selective dopamine uptake inhibitor, D-84, suppresses cocaine self-administration, but does not occasion cocaine-like levels of generalization.

A successful replacement pharmacotherapy for treating cocaine dependency would likely reduce cocaine's abuse, support a low abuse liability, overlap cocaine's subjective effects, and have a long duration of action. Inhibitors with varying selectivity at the dopamine transporter (DAT) have approximated these properties. The objective of the present study was to characterize the behavioural effects of an extremely selective DAT inhibitor, (+) trans-4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl) piperadin-3-ol (D-84), a 3-hydroxy substituted piperidine derivative of GBR-12935, for its cocaine-like discriminative stimulus effects, its effects on cocaine self-administration, and for its own self-administration.

Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

A novel series of optically active molecules based on a 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.

Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.

Rationale: Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists.

Objective: It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice.

Methods: Adult male Sprague-Dawley rats were trained to discriminate 0.

Nicotine physical dependence and tolerance in the mouse following chronic oral administration.

Rationale: Although nicotine dependence and tolerance develop in rats, few studies have examined these processes in the mouse. Establishing such mouse models would eventually allow for an examination of the role of specific nicotinic receptor subtypes in mediating these processes (i.e.