Chronic binge-like moderate ethanol drinking in rats results in widespread decreases in brain serotonin, dopamine, and norepinephrine turnover rates reversed by ethanol intake.

This research was initiated to assess the turnover rates (TORs) of dopamine (DA), norepinephrine (NA), serotonin (5-HT), aspartate, glutamate, and GABA in brain regions during rodent ethanol/sucrose (EtOH) and sucrose (SUC) drinking and in animals with a history of EtOH or SUC drinking to further characterize the neuronal systems that underlie compulsive consumption. Groups of five male rats were used, with two trained to drink EtOH solutions, two to drink SUC and one to serve as a non-drinking control. When stable drinking patterns were obtained, rats were pulse labeled intravenously and killed 60 or 90 min later and the TORs of DA, norepinephrine, 5-HT, aspartate, glutamate, and GABA determined in brain regions.

Micro-opioid receptor alkylation in the ventral pallidum and ventral tegmental area, but not in the nucleus accumbens, attenuates the effects of heroin on cocaine self-administration in rats.

The concurrent use of cocaine and heroin, often referred to as speedball, is a powerful reinforcer that has been reported in humans to sometimes result in heightened euphoria compared with either drug alone. Data from animal research indicate that the reinforcing efficacy of low doses of cocaine is potentiated by the addition of small amounts of heroin and that this potentiation is accompanied by synergistic increases in nucleus accumbens (NAc) extracellular fluid levels of dopamine. Although micro- and/or delta-opioid receptors may underlie this potentiation, the opioid receptor subtype or the loci responsible for this enhancement is not known.

Self-administered heroin and cocaine combinations in the rat: additive reinforcing effects-supra-additive effects on nucleus accumbens extracellular dopamine.

The concurrent use of cocaine and opiate combinations (speedball) has increased since the 1970s and now represents a growing subset of intravenous drug abusers. An isobolographic analysis was applied to the ascending limb of the dose-effect curves for rat self-administration of cocaine, heroin, and their combination to determine the nature of the interaction. The addition of heroin to cocaine shifted the dose-effect curve for self-administration to the left, and the modulation in reinforcing efficacy of the combination of cocaine and heroin was found to be additive.

Involvement of cholinergic neuronal systems in intravenous cocaine self-administration.

Recent studies suggest the participation of cholinergic neurons in the brain processes underlying reinforcement. The involvement of cholinergic neurons in cocaine self-administration has been recently demonstrated in studies using muscarinic and nicotinic agonists and antagonists, microdialysis, assessment of choline acetyltransferase activity and acetylcholine (ACh) turnover rates. The present experiment was initiated to identify subsets of cholinergic neurons involved in the brain processes that underlie cocaine self-administration by lesioning discrete populations with a selective neurotoxin.

Acetylcholine turnover rates in rat brain regions during cocaine self-administration.

The involvement of cholinergic neurons in the brain processes underlying reinforcement has been recently demonstrated. This experiment assessed the potential role of cholinergic neurons in cocaine reinforcement by measuring the turnover rates of acetylcholine in brain regions of rats self-administering cocaine and in yoked cocaine and yoked vehicle-infused controls. The activity of cholinergic innervations of and/or interneurons in the olfactory tubercle, caudate putamen, diagonal band-pre-optic region, ventral pallidum, lateral and medial hypothalamus, hippocampus, ventral tegmental area and visual cortices reflected by the turnover rates of acetylcholine were significantly altered in rats self-administering cocaine compared to yoked cocaine infused controls.

Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.

Rationale: Neurotoxin induced lesions of dopamine-releasing neurons that innervate the nucleus accumbens (NAcc) alter cocaine self-administration. In addition, elevated extracellular levels of NAcc dopamine (DA) are thought to be central to the biological mechanisms that underlie this behavior.

Objectives: This study assessed the long-term effects of 6-hydroxydopamine (6-OHDA) induced lesions of the NAcc on cocaine self-administration and the dialysate levels of dopamine ([DA](d)) in this structure to determine if recovery of drug intake was correlated with the DA response.