Dopamine hypothesis

Spanagel R, Weiss F (1999) The dopamine hypothesis of reward past and current status. Trends Neurosci 22 521-527... 

The increased dopamine hypothesis is supported by findings of gene induction in the target areas and the indications that individual differences in dopamine receptors and transporters may underlie impulsive and addictive behaviour in humans. Studies in knock-out mice have, however, provided evidence for complex roles of 5-HT in these processes. 

Carlsson, A. (1988). The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1(3), 179-86. 

Clemens S., Rye D., Hochman S. (2006). Restless legs syndrome revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 67, 125-30. 

Kuhar M., Ritz M., Boja J. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci. 14 299, 1991. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

The D2 antagonist activity of current antipsychotics led to the "dopamine hypothesis," which states that the pathophysiology of schizophrenia is due to excessive dopaminergic neurotransmission and dysfunctional D2 signaling [6]. This hypothesis has prevailed for nearly 60 years however, it falls short as a complete explanation due to the deficiencies current antipsychotics exhibit against negative and cognitive symptoms. 

The dopamine hypothesis has dominated schizophrenia research for over 40 years 880... 

Determining the underlying rationale for studying a neuroreceptor system, e.g. the dopamine hypothesis for cocaine abuse and schizophrenia ... 

Seeman P. (1987). Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse. 

Three hypotheses have been put forward to account for central fatigue the hypoglycaemic hypothesis the dopamine hypothesis and the 5-hydroxytryptamine hypothesis. 

However, the dopamine hypothesis does not account for some important observations. If an abnormality of dopamine physiology were solely responsible for the pathogenesis of schizophrenia, antipsychotic drugs would do a much better job in treating patients. As it is, they are only partially effective for most and ineffective for some patients. Moreover, there is evidence that diminished glutamatergic activity also plays a role in... 

In 1976, Ian Creese, David R. Burt, and Solomon H. Snyder of Johns Hopkins University in Baltimore, Maryland, reported that the most effective schizophrenia medications are the ones that have the strongest affinity for dopamine receptors. Researchers also discovered drugs that increased the amount of dopamine inadvertently caused schizophrenic symptoms in patients. These findings led to the dopamine hypothesis of schizophrenia—too much dopamine causes schizophrenia. 

Dutch researcher Jacques van Rossum proposes the dopamine hypothesis of schizophrenia, which attributes the symptoms of the disease to an excess of dopamine. 

After long-term administration, antidepressants may enhance dopaminergic neurotransmission, even if direct acute effects are absent (Serra et al. 1990b). For example, the stress-induced decrease in the binding of quinpirole, an agonist of Dj and Dj receptors, can be reversed by chronic imipramine treatment [Papp et al. 1994). These and related data, however, do not allow the formulation of a dopamine hypothesis of depression, but rather point to a role for decreased dopaminergic neurotransmission in specific neuronal circuits that are responsible for those depressive syndromes associated with motivational loss, psychomotor retardation, and anhedonia [Willner 1995). 

Oppenheim G Estrogen in the treatment of depression neuropharmacological mechanisms. Arch Gen Psychiatry 43 569-573, 1986 Oren DA, Moul DE, Schwartz PJ, et al A controlled trial of levodopa plus carbidopa in the treatment of winter seasonal affective disorders a test of the dopamine hypothesis. J Chn Psychopharmacol 14 196-200, 1994 Ormandy G, Jope RS Analysis of the convulsant-potentiating effects of lithium in rats. Exp Neurol 111 356-361, 1991... 

Randrup A, Braestrup C Uptake inhibition of biogenic amines by newer antidepressant drugs relevance to the dopamine hypothesis of depression. Psychopharmacology 53 309-314, 1977... 

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