Reward amphetamine

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. 

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. 

Garden City, NY, Medical Examination Publishing, 1981 Snyder SH, Faillace L 2,3-Dimethoxy-4-methyl-amphetamine (STP) a new hallucinogenic drug. Science 1388 669-670, 1967 Spielewoy C, Markou A Withdrawal from chronic phencyclidine treatment induces long-lasting depression in brain reward function. Neuropsychopharmacology 28 1106-1116,2003... 

Most of the motor effects of amphetamine, especially stereotypy, are due to the release of DA as are its psychotic effects such as hallucinations. Its ability to mimic the action of DA in reward and reinforcement behaviour may contribute to its abuse potential (see Chapter 22) but its arousal (stimulant) properties also involve NA release. 

The stimulation of locomotor activity by MDMA and the importance of mesolimbic dopamine in this response reflect similarities with the prototype phenylethylamine stimulant, amphetamine. It is important to note that these parameters are frequently associated with rewarding aspects of drugs and drug abuse. Additionally, the behavioral profiles of MDMA and I E share certain characteristics with hallucinogen-Iike agents. This unique mixture of stimulus properties and neurochemical actions may contribute to a dangerous behavioral toxicity and neurotoxic potential for drugs like MDMA. 

Yokel, R.A., and Wise, R.A. Increased lever pressing for amphetamine after pimozide in rats Implications for a dopamine theory of reward. Science 187 547-549, 1975. 

Ventura R., Cabib S., Alcaro A., Orsini C., Puglisi-AUegra S. (2003). Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release. J. Neurosci. 23, 1879-85. 

Sellings, L.H. and Clarke, P.B., Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core, J. Neurosci., 23, 6295, 2003. 

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... 

FIGURE 56-1 Major drug classes, structures of prototypical agonists and primary targets implicated in drug class reward. See Figure 56-4 for structures of amphetamines. 

Liechti ME, Markou A (2007) Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats. Eur J Pharmacol 554 164-174 Lin D, Koob GP, Markou A (2000) Time-dependent alterations in ICSS thresholds associated with repeated amphetamine administrations. Pharmacol Biochem Behav 65 407-417... 

Wyvell CL, Berridge KC (2000) Intra-accumbens amphetamine increases the pure incentive salience of a Pavlovian cue for food reward enhancement of wanting without either liking or reinforcement, J Neurosci 20 8122-8130... 

Carr GD, PhtUips AG, et al (1988) Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference. Psychopharmacology 94(2) 221-226 Chaudhri N, Caggiula AR, et al (2005) Sex differences in the contribution of nicotine and non-pharmacological stimuh to nicotine setf-administration in rats. Psychopharmacology 180(2) 258-266... 

Harrison AA, Liem YT, Markou A (2001) Fluoxetine combined with a serotonin-lA receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats. Neuropsychopharmacology 25 55-71... 

In an examination of the effects of low doses of ondansetron on acquisition of responding for a conditioned reward and on the response-potentiating effect of amphetamine in the rat, ondansetron had no effect on the learning of stimulus reward relationships but caused a small attenuation of the amphetamine effect, suggesting a possible modulatory role for 5-HTj receptors in this process (P. J. Fletcher and Higgins 1997]. 

Inhibition of conditioned (but not unconditioned) avoidance behavior is one of the most predictive tests of antipsychotic action. Another is the inhibition of amphetamine- or apomorphine-induced stereotyped behavior. Other tests that may predict antipsychotic action are reduction of exploratory behavior without undue sedation, induction of a cataleptic state, inhibition of intracranial self-stimulation of reward areas, and prevention of apomorphine-induced vomiting. Most of these tests are difficult to relate to any model of clinical psychosis. 

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