Differential regulation of accumbal dopamine transmission in rats following cocaine, heroin and speedball self-administration

• Published in: Journal of neurochemistry 2012-07, Vol.122 (1), p.138-146
• Main Authors: Pattison, Lindsey P., McIntosh, Scot, Budygin, Evgeny A., Hemby, Scott E.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cocaine; Cocaine - administration & dosage; Conditioning, Operant - drug effects; Dopamine; Dopamine - metabolism; Dopamine Uptake Inhibitors - administration & dosage; Drug addiction; Drug Combinations; Electrochemistry; Fundamental and applied biological sciences. Psychology; Heroin; Heroin - administration & dosage; Infusions, Intraventricular; Male; Medical sciences; Microdialysis; Narcotics - administration & dosage; Neurochemistry; Nucleus Accumbens - drug effects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Inbred F344; Reinforcement Schedule; Rodents; Self Administration; speedball; Time Factors; Vertebrates: nervous system and sense organs; voltammetry
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2012.07738.x

J. Neurochem. (2012) 122, 138–146. Cocaine/heroin combinations (speedball) exert synergistic neurochemical and behavioral effects that are thought to contribute to the increased abuse potential and subjective effects reported by polydrug users. In vivo fast‐scan cyclic voltammetry was used to examine the effects of chronic intravenous self‐administration (25 consecutive sessions) of cocaine (250 μg/inf), heroin (4.95 μg/inf) and speedball (250/4.95 μg/inf cocaine/heroin) on changes in electrically evoked dopamine (DA) efflux, maximal rate of DA uptake (Vmax) and the apparent affinity (Km) of the DA transporter in the nucleus accumbens. The increase in electrically evoked DA was comparable following cocaine and speedball injection; however, heroin did not increase evoked DA. DA transporter Km values were similarly elevated following cocaine and speedball, but unaffected by heroin. However, speedball self‐administration significantly increased baseline Vmax, while heroin and cocaine did not change baseline Vmax, compared with the baseline Vmax values of drug‐naïve animals. Overall, elevated DA clearance is a likely consequence of synergistic elevations of nucleus accumbens extracellular DA concentrations by chronic speedball self‐administration, as reported previously in microdialysis studies. The present results indicate neuroadaptive processes that are unique to cocaine/heroin combinations and cannot be readily explained by simple additivity of changes observed with cocaine and heroin alone. Speedball Self‐administration Increases DAT‐mediated Reuptake Rate 
Fast‐scan cyclic voltammetry was used to investigate the effects of chronic cocaine, heroin and speedball self‐administration on the dynamics of dopamine neurotransmission within the nucleus accumbens. Speedball self‐administration significantly increased baseline rates of DAT‐mediated reuptake (Vmax). The present results indicate neuroadaptive processes that are unique to cocaine/heroin combinations and cannot be readily explained by simple additivity of changes observed with cocaine or heroin alone.