The present study examined the role of nitric oxide in cocaine-induced apoptosis in bovine coronary artery endothelial cells (BCAECs). Cocaine produced a time-dependent decrease in cell viability and an increase in apoptosis in BCAECs, which were blocked by the nitric oxide donors DETA-NONOate (DETA-NO) and S-nitroso-N-acetyl-penicillamine. In accordance, cocaine decreased nitric oxide producti...

BACKGROUND Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. METHODS Seventeen non-treatment seeking, cocaine-dependent volunteers pa...

Reinforcement-Related Regulation of AMPA Glutamate Receptor Subunits in the Ventral Tegmental Area Enhances Motivation for Cocaine Chronic cocaine use produces numerous biological changes in brain, but relatively few are functionally associated with cocaine reinforcement. Here the authors show that daily intravenous cocaine self-administration, but not passive cocaine administration, induces dy...

Social partners influence the likelihood of using drugs, developing a substance use disorder and relapse to drug use after a period of abstinence. Preclinical studies report that social cues influence the acquisition of cocaine use, the escalation of cocaine use over time, and the compulsive patterns of cocaine use that emerge during an extended binge. The purpose of this study was to examine t...

BACKGROUND AND PURPOSE The stress-related neuropeptide, corticotropin-releasing factor (CRF), has become an important focus of studies of cocaine addiction, and in particular, the effects of stress on cocaine-related behaviours. A recently discovered peptide system, the teneurin C-terminal associated peptides (TCAP), has been implicated in the regulation of the stress response, via a CRF-relate...

Cocaine abuse increases the risk of life-threatening neurological complications such as strokes and seizures. Although the vasoconstricting properties of cocaine underlie its cerebrovascular effects, the mechanisms underlying its neurotoxicity remain incompletely understood. Here, we use optical techniques to measure cerebral blood volume, hemoglobin oxygenation (S(t)O(2)), and intracellular ca...

Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mech...

Cocaine is one of the most addictive drugs, and there is still no FDA (Food and Drug Administration)-approved medication specific for cocaine abuse. A promising therapeutic strategy is to accelerate cocaine metabolism, producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in ...

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic vol...

The effects of i.v. cocaine self-administration under "naturalistic" conditions on plasma corticosterone (CORT) and prolactin (PRL) were investigated in male Sprague-Dawley rats. After the determination of plasma CORT and PRL levels under basal conditions before access to cocaine for self-administration, rats were allowed to self-administer cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg/infusion i.v.) b...