Editorial: Dopaminergic Alterations in Schizophrenia

Tricklebank, Mark D.; Tamminga, Carol A.; Grottick, Andrew J.; Llorca, Pierre Michel; McArthur, Silvia Gatti; Martel, Jean Claude

doi:10.3389/fnins.2021.663245

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…Soon after discovering the receptor, Seeman et al [ 39 , 40 ] showed that the published clinical doses of all antipsychotic drugs available at the time, regardless of their molecular structure, directly correlated with their ability to displace radioactive haloperidol[ 39 , 40 ]. This graph has recently been called “the most famous graph in schizophrenia therapeutics.”[ 41 ]. The findings from the Seeman laboratory were soon confirmed by binding studies from other labs[ 42 - 44 ].…”

Section: Historymentioning

confidence: 99%

History of the dopamine hypothesis of antipsychotic action

Seeman¹

2021

WJP

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The dopamine hypothesis of how antipsychotic drugs exert their beneficial effect in psychotic illness has an interesting history that dates back to 1950. This hypothesis is not to be confused with the dopamine hypothesis of schizophrenia; the aim of the latter is to explain the etiology of schizophrenia. The present review does not deal with schizophrenia but, rather, with the historical development of our current understanding of the dopamine-associated actions of the drugs that reduce the symptoms of psychosis. This historical review begins with the serendipitous discovery of chlorpromazine, a drug synthesized around a chemical core that initially served to produce man-made dyes. This molecular core subsequently contributed to the chemistry of antihistamines. It was with the aim of producing a superior antihistamine that chlorpromazine was synthesized; instead, it revolutionized the treatment of psychosis. The first hypothesis of how this drug worked was that it induced hypothermia, a cooling of the body that led to a tranquilization of the mind. The new, at the time, discoveries of the presence of chemical transmitters in the brain soon steered investigations away from a temperature-related hypothesis toward questioning how this drug, and other drugs with similar properties and effects, modulated endogenous neurotransmission. As a result, over the years, researchers from around the world have begun to progressively learn what antipsychotic drugs do in the brain.

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Section: Historymentioning

confidence: 99%

History of the dopamine hypothesis of antipsychotic action

Seeman¹

2021

WJP

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“…Phil also showed that the clinically effective doses of all antipsychotic medications available at the time, regardless of their molecular structure, directly correlated with the drug's ability to displace radioactive haloperidol (Seeman, Lee, Chau-Wong, & Wong, 1976 ). The graph that accompanied this 1976 paper has been called, as recently as this year, ‘the most famous graph in schizophrenia therapeutics’ (Tricklebank et al, 2021 ).…”

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confidence: 99%

Philip Seeman's contributions to the story of schizophrenia

Seeman

2022

Psychol. Med.

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Neurobehavioral Profiles of Six Genetically-based Rat Models of Schizophrenia- related Symptoms

Oliveras

Cañete

Sampedro-Viana

et al. 2023

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Schizophrenia is a chronic and severe mental disorder with high heterogeneity in its symptoms clusters. The effectiveness of drug treatments for the disorder is far from satisfactory. It is widely accepted that research with valid animal models is essential if we aim at understanding its genetic/neurobiological mechanisms and finding more effective treatments. The present article presents an overview of six genetically-based (selectively-bred) rat models/strains, which exhibit neurobehavioral schizophrenia- relevant features, i.e., the Apomorphine-susceptible (APO-SUS) rats, the Low-prepulse inhibition rats, the Brattleboro (BRAT) rats, the Spontaneously Hypertensive rats (SHR), the Wisket rats and the Roman High-Avoidance (RHA) rats. Strikingly, all the strains display impairments in prepulse inhibition of the startle response (PPI), which remarkably, in most cases are associated with novelty-induced hyperlocomotion, deficits of social behavior, impairment of latent inhibition and cognitive flexibility, or signs of impaired prefrontal cortex (PFC) function. However, only three of the strains share PPI deficits and dopaminergic (DAergic) psychostimulant-induced hyperlocomotion (together with prefrontal cortex dysfunction in two models, the APO- SUS and RHA), which points out that alterations of the mesolimbic DAergic circuit are a schizophrenia-linked trait that not all models reproduce, but it characterizes some strains that can be valid models of schizophrenia-relevant features and drug-addiction vulnerability (and thus, dual diagnosis). We conclude by putting the research based on these genetically-selected rat models in the context of the Research Domain Criteria (RDoC) framework, suggesting that RDoC-oriented research programs using selectively-bred strains might help to accelerate progress in the various aspects of the schizophrenia-related research agenda.

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Editorial: Dopaminergic Alterations in Schizophrenia

Cited by 3 publications

References 7 publications

History of the dopamine hypothesis of antipsychotic action

History of the dopamine hypothesis of antipsychotic action

Philip Seeman's contributions to the story of schizophrenia

Neurobehavioral Profiles of Six Genetically-based Rat Models of Schizophrenia- related Symptoms

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