The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinica...

The regulation of dopamine and serotonin synthesis in rat brain striatal synaptosomes has been studied using HPLC methods. Noradrenaline was shown to markedly inhibit both the synthesis of dopamine and serotonin. The response of the synaptosomes to the concentrations of noradrenaline appeared to be biphasic, a very effective inhibition occurring at low concentrations (1-5 µm) and a relativ...

Glutamate overactivity within the basal ganglia has been shown to be central to the expression of motor symptoms in advanced stages of Parkinson's disease, and metabotropic glutamate receptors (mGluRs) represent promising targets for new therapeutic strategies in this pathology. Little is known, however, about the cellular and behavioral changes occurring in the early stages of the disease when...

Methotrexate may cause seizures, dementia, and leukoencephalopathy when given in toxic doses to children with leukemia or solid tumors. Even in therapeutic doses, treatment with this drug is associated with an increased incidence of seizures in children with leukemia. To study mechanisms of injury, juvenile rats were given multiple intraventricular injections of methotrexate and the brains were...

Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across mult...

Recent findings suggest the reward system encodes metabolic value independent of taste, provoking speculation that the hedonic value of taste could be derived from nutritional value as a secondary appetitive property. We therefore dissociated and compared the impact of nutrition and taste on appetitive behavior in several paradigms. Though taste alone induces preference and increased consumptio...

Dopamine-releasing neurons within the Substantia nigra (SN DA) are particularly vulnerable to degeneration compared to other dopaminergic neurons. The age-dependent, progressive loss of these neurons is a pathological hallmark of Parkinson's disease (PD), as the resulting loss of striatal dopamine causes its major movement-related symptoms. SN DA neurons release dopamine from their axonal termi...

The goal of this review is to demonstrate the role of metabolic variations in estrogen metabolism and polymorphisms in enzymatic control in the oncogenesis of breast and prostate cancer and Parkinsonism. Further biochemical associations with these cancers are demonstrated. The evidence for interference of oncogenic metabolites by certain anti-oxidants is reviewed. The role of endogenous hormone...