Reward cocaine

Kometsky, Conan, and Christine Duvauchclle. 1994. "Dopamine, a Common Substrate for the Rewarding Effects of Brain Stimulation Reward, Cocaine, and Morphine." National Institute on Drug Abuse Research Monograph Series 145 19-39. 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

Lepore M, Vorel SR, Lowinson J, et al Conditioned place preference induced by delta-9-tetrahydrocannabinol comparison with cocaine, morphine, and food reward. LifeSci 56 2073-2080, 1995... 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

The development of effective pharmacotherapy has lagged behind progress in understanding the reward mechanisms and chronic impairments underlying stimulant abuse. Pharmacological and behavioral treatment approaches that have been used for cocaine abuse have not been as widely tested for the treatment of amphetamine abuse, limiting what can be offered for treatment of this disorder. No treatment agents are approved by the FDA for treatment of cocaine or amphetamine dependence. 

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

Arnold, L.E. Kirilcuk, V. Corson, S.A. and Corson, E.O. Levoampheta-mine and dextroamphetamine Differential effect on aggression and hyperkinesis in children and dogs. Am J Psychiatry 130 165-170, 1973. Bain, G.T., and Kometsky, C. Naloxone attenuation of the effect of cocaine on rewarding brain stimulation. Life Sci 40 1119-1125, 1987. 

The neuroehemical sites for psyehomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus aeeumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intraeranial self-administration of eoeaine is elicited from the frontal cortex, but not from the nucleus aeeumbens (Goeders and Smith 1983). Thus, eoneomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983 Smith et al. 1982). 

McClung C., Sidiropoulou K, Vitaterna M. et al (2005). Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc. Natl. Acad. Sci. USA 102, 9377-81. 

Figure 1.1 The dopamine transporter terminates the action of released dopamine by transport back into the presynaptic neuron. Dopamine transport occurs with the binding of one molecule of dopamine, one chloride ion, and two sodium ions to the transporter the transporter then translocates from the outside of the neuronal membrane into the inside of the neuron.22 Cocaine appears to bind to the sodium ion binding site. This changes the conformation of the chloride ion binding site thus dopamine transport does not occur. This blockade of dopamine transport potentiates dopaminergic neurotransmission and may be the basis for the rewarding effects of cocaine.

Nakagawa, T., Fujio, M., Ozawa, T., Minami, M., Satoh, M. Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice. 

Beitner-Johnson, D., Nestler, E.J. Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions. J. Neurochem. 57 344, 1991. 

Hiroi, N., Brown, J.R., Haile, C.N. et al. FosB mutant mice loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine s psychomotor and rewarding effects. Proc. Natl. Acad. Sci. U.S.A. 94 10397, 1997. 

Valjent, E., Corvol, J.C., Pages, C. et al. Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J. Neurosci. 20 8701, 2000. 

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