dopamine hypothesis of hallucinatory activity

   Dopamine is also referred to as 3-hydroxytyra-mine, C₆H₃(OH)₂-CH₂-CH₂-NH₂,and 4-(2- aminoethyl)benzene-1,2-diol. The name dopamine is a contraction of the terms d(i)o(xy)p(henyl)a(lanine) and amine. The dopamine hypothesis constitutes a biochemical explanatory model for the mediation of hallucinations and other psychotic phenomena that attributes a central - although by no means exclusive - role to the action ofdopamine within the CNS. Dopamine is classified chemically as a monoamine of the catecholamine family. It has a physiological function in both vertebrates and invertebrates, as a hormone, and as a neuro-transmitter. In humans it is produced by various structures in the CNS, including the substantia nigra, and the ventral tegmental area. As a neurohormone, it is released by the hypothalamus. Dopamine was first synthesized in 1910 by the British chemists George Barger (1878-1939) and James Ewens. Its natural occurrence in the human CNS was demonstrated in 1957 by the Swedish pharmacologists Arvid Carlsson (b. 1923) and Nils-Âke Hillarp (1916-1965). In 1974 the group headed by the American psychiatrist and pharmacologist Solomon H. Snyder (b. 1938) put forward the hypothesis that excess activity of dopamine may play a crucial role in the mediation of hallucinations and other psychotic phenomena. The group based their hypothesis on the discovery that chlorpromazine and other antipsychotic drugs of the phenothiazine class attach themselves to the postsynaptic dopamine receptor, and in this way appear to reduce the neurotransmitter's excitatory effect upon the mesolimbic pathways and other parts of the CNS. One of the virtues of Snyder's work was that it integrated many of the major historical discoveries in this area of research, including the conceptualization of chemical synaptic transmission by the German physiologist Emil du Bois-Reymond (1818-1896) in 1877, the empirical confirmation of the presence of neurotransmitters in the brain by the American biologist Betty Twarog in 1952, and the identification of dopamine as a neurotransmitter in the CNS by Carlsson et al. An additional, and in a sense complementary strand of research that paved the way for Snyder's work was the study of the effects of pro-dopaminergic substances such as cocaine and the amphetamines upon the CNS. Although the dopamine hypothesis still serves as an attractive explanatory model for the mediation of hallucinations and other psychotic phenomena, the initial hope of a one-on-one relationship between dopamine and psychosis was not confirmed. It is now generally held that other neurotransmitters (notably glutamate and serotonin) may play a role in the mediation of psychosis as well. Moreover, it has long been a mystery why the response rate of individuals with psychotic symptoms to any antipsychotic agent lies no higher than 50-60% on average, and why the blockade of dopamine D2 receptor-mediated transmission (which can be obtained within hours after the administration of antipsychotic agents) is usually followed by a significant reduction in psychotic symptoms after a period of only weeks to months. These empirical findings have prompted a shift in focus from 'fast' receptor blockade towards issues such as intracellular signalling, indirect effects, and neuroplasticity. However, arguably the most intriguing - and as yet unresolved - issue remains the exact influence of neurotransmitters such as dopamine upon perception.

   References

   Carlsson, A., Lecrubier, Y., eds. (2004). Progress in dopamine research in schizophrenia. A guide for physicians. London: Taylor & Francis.

   Carlsson, A., Lindqvist, M., Magnussen, T., Waldeck, B. (1958). On the presence of 3-hyd-roxytyramine in the brain. Science, 127, 471.

   Carlsson, A., Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on the formation of 3-methoxythyramine and normetanephrine in mouse brain. Acta Pharmacologica, 20, 140-144.

   Shorter, E. (1997). A history of psychiatry. From the era ofthe asylum to the age ofProzac. New York, NY: John Wiley & Sons.

   Snyder, S.H., Banerjee, S.P., Yamamura, H.I., Greenburg, D. (1974). Drugs, neurotrans-mitters, and schizophrenia. Science, 184, 1243-1253.