Neuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [www.syphad.org]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug–target interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug–target interactions.
Sex differences in behavioural patterns of drug abuse and dependence have been hypothesized to be a consequence of sexual dimorphisms in brain pathways, particularly within the dopaminergic reward circuitry. Yet, how potential sex differences are manifested at a neurochemical level remains unclear. Here, we use a meta‐analysis approach to investigate whether animal studies robustly indicate a different regulation of striatal dopamine transmission in males and females. Data from 39 microdialysis experiments on female rats (n = 676) were extracted and statistically compared with data from 1523 male rats. All drugs of abuse, independent of their molecular mechanisms of action, notably increase extracellular dopamine concentrations in the nucleus accumbens (NAc) and caudate putamen (CPu). No significant sex differences in basal levels or in dopaminergic response to drugs of abuse were found. However, basal dopamine levels in CPu (but not NAc) were significantly altered by ovariectomy. In conclusion, there are no sex‐dependent differences in basal dopamine levels within the NAc and CPu. Previously reported sex differences in the CPu seem to be a result of ovariectomy and may only to a lesser, non‐significant degree be attributed to a sexual duality.
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