Reward cocaine effects

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 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. 

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. 

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. 

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. 

Shippenberg T., Heidbreder C. Sensitization to the conditioned rewarding effects of cocaine pharmacological and temporal characteristics. J. Pharmacol. Exp. Ther. 273 808, 1995. 

Shippenberg T., Heidbreder C. Kappa opioid receptor agonists prevent sensitization to the rewarding effects of cocaine. NIDA Res. Monogr. 153 456, 1994. 

Control of feeding behavior involves peripheral peptides (insulin, ghrelin, leptin) plus several peptides in the CNS (orexins/hypocretins, CCK, galanin, MSH, neuropeptide Y, CRH, cocaine-and-amphetamine-regulated transcript (CART)) [35, 36]. Some of the same peptides are involved in reward systems crucial to drug addiction. Specific receptor blockers are being tested for many of these peptide-receptor systems, with the hope of very selective actins with minimal side effects [35], For example, there are two CCK receptor subtypes, CCK-A and... 

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