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      The dopamine hypothesis of reward: past and current status.

      Trends in Neurosciences
      Dopamine, physiology, Humans, Limbic System, Mesencephalon, Models, Neurological, Reward

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          Abstract

          Mesolimbic dopaminergic neurons are thought to serve as a final common neural pathway for mediating reinforcement processes. However, several recent findings have challenged the view that mesolimbic dopamine has a crucial role in the maintenance of reinforcement processes, or the subjective rewarding actions of natural rewards and drugs of abuse. Instead, there is growing evidence that dopamine is involved in the formation of associations between salient contextual stimuli and internal rewarding or aversive events. This evidence suggests that dopaminergic-neuron activation aids the organism in learning to recognize stimuli associated with such events. Thus, mesolimbic dopaminergic neurons have an important function in the acquisition of behavior reinforced by natural reward and drug stimuli. Furthermore, long-lasting neuroadaptive changes in mesolimbic dopamine-mediated transmission that develop during chronic drug use might contribute to compulsive drug-seeking behavior and relapse.

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          Most cited references48

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          Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.

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            Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

            The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.
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              Drugs of abuse: anatomy, pharmacology and function of reward pathways.

              Drugs of abuse are very powerful reinforcers, and even in conditions of limited access (where the organism is not dependent) these drugs will motivate high rates of operant responding. This presumed hedonic property and the drugs' neuropharmacological specificity provide a means of studying the neuropharmacology and neuroanatomy of brain reward. Three major brain systems appear to be involved in drug reward--dopamine, opioid and GABA. Evidence suggests a midbrain-forebrain-extrapyramidal circuit with its focus in the nucleus accumbens. Data implicating dopamine and opioid systems in indirect sympathomimetic and opiate reward include critical elements in both the nucleus accumbens and ventral tegmental areas. Ethanol reward appears to depend on an interaction with the GABAA receptor complex but may also involve common elements such as dopamine and opioid peptides in this midbrain-forebrain-extrapyramidal circuit. These results suggest that brain reward systems have a multidetermined neuropharmacological basis that may involve some common neuroanatomical elements.
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                Author and article information

                Journal
                10529820
                10.1016/S0166-2236(99)01447-2

                Chemistry
                Dopamine,physiology,Humans,Limbic System,Mesencephalon,Models, Neurological,Reward
                Chemistry
                Dopamine, physiology, Humans, Limbic System, Mesencephalon, Models, Neurological, Reward

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