Paulsen, R. T. | Search bioRxiv

bioRxiv2021

Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.

neuroscience↗

bioRxiv2020

A Draft Reference Genome for Hirudo verbana, the Medicinal Leech

The medicinal leech, Hirudo verbana, is a powerful model organism for investigating fundamental neurobehavioral processes. The well-documented arrangement and properties of H. verbanas nervous system allows changes at the level of specific neurons or synapses to be linked to physiological and behavioral phenomena. Juxtaposed to the extensive knowledge of H. verbanas nervous system is a limited, but recently expanding, portfolio of molecular and multi-omics tools. Together, the advancement of genetic databases for H. verbana will complement existing pharmacological and electrophysiological data by affording targeted manipulation and analysis of gene expression in neural pathways of interest. Here, we present the first draft genome assembly for H. verbana, which is approximately 250 Mbp in size and consists of 61,282 contigs. Whole genome sequencing was conducted using an Illumina sequencing platform followed by genome assembly with CLC-Bio Genomics Workbench and subsequent functional annotation. Ultimately, the diversity of organisms for which we have genomic information should parallel the availability of next generation sequencing technologies to widen the comparative approach to understand the involvement and discovery of genes in evolutionarily conserved processes. Results of this work hope to facilitate comparative studies with H. verbana and provide the foundation for future, more complete, genome assemblies of the leech.

genomics↗