Event Abstract

“Over the moon” or “down in the dumps”? Contradictory effects of chronic adolescent exposure to HU-210 on depressive-like behavior

  • 1 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal
  • 2 Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal

Chronic adolescent exposure to cannabinoid receptor (CBR) agonists has been demonstrated to induce persistent changes in adult rodent behavior, in both the cognitive (i.e., memory impairments) and affective (i.e., depressive-like phenotypes) domains. However, a recent study from our lab, using the potent CBR agonist HU-210, could not replicate this deleterious effect on adult affective functioning. Here, we report two experiments designed to determine if these unexpected results were either due to the effects of HU-210 having reverted to normality during drug washout, or due to treatment not inducing behavioral alterations. For this, adolescent female Sprague-Dawley rats received twice-daily intraperitoneal injections of HU-210 for 11 days in an escalating dosing schedule (PND35-37:25μg/kg; PND38-41:50μg/kg; PND42-45:100μg/kg). Behavioral testing was performed the day after drug administration ended. One series of animals was tested in the Open Field (OFT) and Modified Forced Swim Tests (mFST), and the other was assessed in the Elevated Plus Maze (EPM), and the Sucrose Preference Test (SPT). After testing ended, samples were collected from the hippocampus, striatum and prefrontal cortex, to evaluate the effects of treatment on CB1 receptor protein levels, through Western Blot. Surprisingly, while HU-210 treatment had marked antidepressant effects in the mFST (i.e., decreased immobility and increased climbing), in the SPT it led to strong pro-depressant effects (i.e., decreased sucrose preference/intake). No differences were found in either the OFT or EPM, suggesting no effect on anxiety-like behavior. Regarding the levels of CB1 receptor protein, no differences were detected in the striatum or prefrontal cortex, but a marked reduction was found in the hippocampus of HU-210-treated animals. These results suggest that chronic adolescent exposure to HU-210 is capable of inducing behavioral alterations, but that these are normalized over time. Moreover, the contradictory alterations found further differentiate HU-210, from other CBR agonists, and call into question the comparability of results obtained by studies using different drugs.

Acknowledgements

Work was supported by Twinning action (SynaNet) from the EU H2020 Programme (project number: 692340) and Fundação para a Ciência e a Tecnologia (project number: PTDC/DTP-FTO/3346/2014). Authors have no conflict of interest to declare.

Keywords: Cannabinoids, adolescence, HU-210, Depression, Anxiety

Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.

Presentation Type: Pitch communication + Poster presentation

Topic: Psychiatric Disorders / Addiction

Citation: Ferreira MF, Fonseca-Gomes J, Rei N, Mouro FM and Sebastião AM (2019). “Over the moon” or “down in the dumps”? Contradictory effects of chronic adolescent exposure to HU-210 on depressive-like behavior. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00027

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Received: 16 Apr 2019; Published Online: 27 Sep 2019.

* Correspondence: Mr. Miguel F Ferreira, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal, jorge.ferreira@medicina.ulisboa.pt

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