Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons in the striatum

PLoS One. 2018 Jul 26;13(7):e0200950. doi: 10.1371/journal.pone.0200950. eCollection 2018.

Abstract

Derivatives from the Cannabis plant are the most commonly abused illegal substances in the world. The main psychoactive component found in the plant, Δ-9-tetrahydrocannabinol (THC), exerts its effects through the endocannabinoid system. Manipulations of this system affect some types of learning that seem to be dependent on dorsal striatum synaptic plasticity. Dendritic spines exhibit important synaptic functional attributes and a potential for plasticity, which is thought to mediate long-lasting changes in behaviour. To study the possible structural plasticity changes that prolonged THC administration might exert in the dorsal striatum, adult, male C57BL6/J mice were intraperitoneally injected with THC (10mg/kg) or vehicle for 15 days followed by a 7-day drug-free period. Using single cell intracellular injections of Lucifer Yellow, confocal microscopy, and 3D reconstruction of labelled neurons, we studied dendritic spine density and spine size in medium spiny neurons (MSNs) of the anterior dorsolateral striatum (aDLS) and posterior dorsomedial striatum (pDMS). We found that the THC treatment increased dendritic spine density in the distal part of the dendrites of MSNs in the pDMS, but no changes were found in the rest of the parameters analysed in either region studied. We also observed that dendritic spines of MSNs of pDMS presented lower volume and surface area values than MSNs of the aDLS. These results seem to indicate that THC could induce structural plasticity alterations in the circuits involving pDMS MSNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Spines / drug effects*
  • Dendritic Spines / metabolism*
  • Dronabinol / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / cytology*

Substances

  • Dronabinol

Grants and funding

Funding for this study was provided by the Spanish Ministry of Health, Social Services and Equality (http://www.pnsd.msssi.gob.es;grant PND-2016I073 to E.A.); the Carlos III Health Institute (http://www.isciii.es; grant RTA-RD16/020/0022 to E.A; the Centre for Networked Biomedical Research into Neurodegenerative Diseases (https://www.ciberned.es; CIBERNED, CB06/05/0066 to J.DF.); the Spanish Ministry of Economy and Competitiveness (http://www.mineco.gob.es/portal/site/mineco/idi; grant SAF 2015-66603-P to J.DF, grant PSI2016-80082-P to MM, and grant PSI80541-P to E.A); the Directorate General of Research of the Autonomous Community of Madrid (https://www.madrimasd.org/madrid-ciencia-tecnologia/convocatorias; grant S-2011/BMD-2308, Activities Programme I+D+I CANNAB-CM to EA); and European Union (https://ec.europa.eu/info/funding-tenders_en; grant JUST/2013/DPIP/AG/4823-EU MADNESS). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.