Cocaine's blockade of dopamine reuptake by brain dopamine transporters (DAT) is a central feature of current understanding of cocaine reward and addiction. Empirical screening of small-molecule chemical libraries has thus far failed to provide successful cocaine blockers that allow dopamine reuptake in the presence of cocaine and provide cocaine "antagonism". We have approached this problem by ...

Cholinergic muscarinic systems have been shown to influence dopaminergic function in the central nervous system. In addition, previous studies of benztropine analogs that inhibit dopamine uptake and show antagonism at muscarinic receptors show these drugs to be less effective than cocaine in producing its various prototypic effects such as locomotor stimulation. Because previous pharmacological...

The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benzoylecgonine (BE) and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg i...

Outbred, male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on cocaine-induced locomotor activity in an open-field arena. This difference reflects cocaine's ability to inhibit the striatal dopamine transporter and predicts development of sensitization. To investigate the relationship between initial cocaine locomotor responsive...

Kalirin-7 (Kal7) is a Rho-guanine nucleotide exchange factor that is localized in neuronal postsynaptic densities. Kal7 interacts with the NR2B subunit of the NMDA receptor and regulates aspects of dendritic spine dynamics both in vitro and in vivo. Chronic treatment with cocaine increases dendritic spine density in the nucleus accumbens (NAc) of rodents and primates. Kal7 mRNA and protein are ...

OBJECTIVES Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal cortex in response to biologically salient stimuli in an emotional face matching task ...

BACKGROUND We previously observed that behavioral economic factors predict naturalistic heroin seeking behavior that correlates with opioid seeking in the experimental laboratory. The present study sought to replicate and extend these prior findings with regular cocaine users. METHODS Participants (N=83) completed a semi-structured interview to establish income-generating and cocaine-purchasi...

The cysteine prodrug N-acetylcysteine (NAC) has been shown to reduce reinstatement of cocaine seeking by normalization of glutamatergic tone. However, enduring inhibition of cocaine seeking produced by NAC has not been explored under different withdrawal conditions. Thus, the present study determined whether chronic NAC administered during daily extinction training or daily abstinence after wit...

Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 3...

In Australia, the lifetime use of cocaine is rising, with 3% of the population aged over 14 using cocaine in 1991, increasing to 4.5% in 1998, and cocaine use accounting for 10% of all deaths secondary to illicit drug use in 1998. Cocaine is prepared from the leaves of the plant Erythroxylon coca, and is available as cocaine hydrochloride (a water-soluble powder or granule which can be taken or...