Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits
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ORIGINAL ARTICLE
Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats Oualid Abboussi 1
&
Zineb Ibn Lahmar Andaloussi 2 & Ajonijebu Duyilemi Chris 3 & Khalid Taghzouti 2
Received: 2 July 2020 / Revised: 28 July 2020 / Accepted: 30 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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, MAOA 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 sensorimotorgating 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 cannabinoidinduced schizoaffective-like behaviour. Keywords Cannabinoids . Adolescence . Schizophrenia . Prepulse inhibition . Dopamine metabolism
Introduction Cannabis is one of the most commonly used illicit drug worldwide, especially during adolescence and early * Oualid Abboussi [email protected] 1
Division of Neuroscience, Ninewells Hospital and Medical School, Institute of Academic Anaesthesia, University of Dundee, Dundee, UK
2
Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University in Rabat, Rabat, Morocco
3
Department of Physiology, School of Biomolecular and Chemical Sciences, Faculty of Science, Nelson Mandela University, Port Elizabeth, South Africa
adulthood (Renard et al. 2014), a developmental stage where the endocannabinoid system reach maximal levels of maturity similar to that described for the dopaminergic system before declining later in life due to post-adolescent pruning (Bossong and Niesink 2010; Long et al. 2012; Rubino et al. 2015). Accumulating clinical evidence emphasi
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