Neurobiological correlates of acute neuroleptic treatment.
The mechanisms behind the antipsychotic actions of neuroleptic drugs are still far from clear. There is general agreement that the antipsychotic action of most if not all neuroleptic drugs is related to their tendency to interact with one or several members of the receptor families for the neurotransmitters dopamine, noradrenaline and serotonin. Currently, dopamine receptor subtypes belonging to the D2 family and several serotonin receptor subtypes are a focus of interest. Receptor effects are induced almost immediately upon the initiation of acute neuroleptic treatment and are generally proportional to the drug concentration in the tissue. Recent work has shown that the expression of neuropeptide genes, immediate early genes and genes for specific subtypes of glutamate receptors is stimulated in distinct regions of the brain during chronic treatment with neuroleptic drugs. These effects appear on time-scales that are similar to the relatively slow induction of antipsychotic action and are therefore of particular interest. In order to understand the mechanisms behind the latency for antipsychotic action these neurobiological correlates must be clarified. The effects can be regarded as a secondary cascade of events, probably initiated and maintained by receptor effects. In the present review, direct effects of neuroleptic drugs on monaminergic receptor subtypes are summarized together with their indirect effects on monoamine release and gene expression. These important findings suggest new targets in the search for the critical brain regions that mediate antipsychotic action.
Sedvall
G C
GC
Department of Clinical Neuroscience, Karolinska Institute and Hospital, Stockholm, Sweden.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017982:Receptors, Biogenic Amine / Q000187:drug effects* / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000276:immunology; D012559:Schizophrenia / Q000188:drug therapy*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D017982:Receptors, Biogenic Amine; D017470:Receptors, Glutamate