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Background  The long-term effects of psychotropic drugs are associated with the reversal of disease-related alterations through the reorganization and normalization of neuronal connections. Molecular factors that trigger drug-induced brain plasticity remain only partly understood. Doublecortin-like kinase 1 ( Dclk1 ) possesses microtubule-polymerizing activity during synaptic plasticity and neurogenesis. However, the  Dclk1  gene shows a complex profile of transcriptional regulation, with two alternative promoters and exon splicing patterns that suggest the expression of multiple isoforms with different kinase activities.    Results  Here, we applied next-generation sequencing to analyze changes in the expression of  Dclk1  gene isoforms in the brain in response to several psychoactive drugs with diverse pharmacological mechanisms of action. We used bioinformatics tools to define the range and levels of  Dclk1  transcriptional regulation in the mouse nucleus accumbens and prefrontal cortex. We also sought to investigate the presence of DCLK1-derived peptides using mass spectrometry. We detected 15 transcripts expressed from the  Dclk1  locus (FPKM > 1), including 2 drug-regulated variants (fold change > 2). Drugs that act on serotonin receptors (5-HT2A/C) regulate a subset of  Dclk1  isoforms in a brain-region-specific manner. The strongest influence was observed for the mianserin-induced expression of an isoform with intron retention. The drug-activated expression of novel alternative  Dclk1  isoforms was validated using qPCR. The drug-regulated isoform contains genetic variants of DCLK1 that have been previously associated with schizophrenia and hyperactivity disorder in humans. We identified a short peptide that might originate from the novel DCLK1 protein product. Moreover, protein domains encoded by the regulated variant indicate their potential involvement in the negative regulation of the canonical DCLK1 protein.    Conclusions  In summary, we identified novel isoforms of the neuroplasticity-related gene  Dclk1  that are expressed in the brain in response to psychotropic drug treatments.    Electronic supplementary material  The online version of this article (10.1186/s12868-018-0458-4) contains supplementary material, which is available to authorized users.

Expression of alternatively spliced variants of the Dclk1 gene is regulated by psychotropic drugs