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Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats

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Abstract

Several lines of evidence suggest that chronic exposure to cannabinoids during adolescence may increase the risk of schizophrenia. Studies of the disorder have identified altered cortical dopaminergic neurotransmission. In this study, we hypothesised that heightened endocannabinoid system activation via chronic exposure to a highly potent cannabinoid receptors agonist in adolescent rats would cause long-lasting neurobiological changes that may dramatically alter expression and functions of dopamine metabolising enzymes, comethyl-o-transferase (COMT) and monoamine oxidases MAO-A and MAO-B. To test this hypothesis, adult male rats (70 PND) undergoing chronic treatment of the highly potent and non-selective CB agonist WIN55,212-2 (1.2 mg/kg) during adolescence (PND 30–50) were subjected after 20 days washout period to prepulse inhibition of acoustic startle test (PPI) to confirm cannabinoid-induced sensorimotor-gating impairments and afterwards examined for COMT, MAO-A and MAO-B expression and activity in the prefrontal cortex. Chronic WIN55,212-2 exposure during adolescence caused disruption of PPI, increased cortical dopamine level, decreased COMT mRNA expression and decreased MAO-A and MAO-B enzymatic activities. These results indicate that chronic exposure to cannabinoids during adolescence induces sensorimotor-gating alterations which likely result from changes in the prefrontal cortex dopaminergic signalling. This has important implications for developing methods of targeting dopamine metabolising enzymes and/or sequelae of its dysregulation in cannabinoid-induced schizoaffective-like behaviour.

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Authors and Affiliations

  1. Division of Neuroscience, Ninewells Hospital and Medical School, Institute of Academic Anaesthesia, University of Dundee, Dundee, UK

    Oualid Abboussi

  2. Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University in Rabat, Rabat, Morocco

    Zineb Ibn Lahmar Andaloussi & Khalid Taghzouti

  3. Department of Physiology, School of Biomolecular and Chemical Sciences, Faculty of Science, Nelson Mandela University, Port Elizabeth, South Africa

    Ajonijebu Duyilemi Chris

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  1. Oualid Abboussi
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  2. Zineb Ibn Lahmar Andaloussi
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  3. Ajonijebu Duyilemi Chris
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  4. Khalid Taghzouti
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Correspondence to Oualid Abboussi.

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Abboussi, O., Andaloussi, Z.I.L., Chris, A.D. et al. Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats. Neurotox Res 38, 682–690 (2020). https://doi.org/10.1007/s12640-020-00266-1

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