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RESEARCH PRODUCT

PHARMACOLOGICAL MODULATION OF OPERANT BEHAVIOUR FOR ACETALDEHYDE. INVOLVEMENT OF D2 AND CB1 RECEPTORS.

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Acetaldehyde (ACD), the first metabolite of ethanol, has rewarding and motivational properties, as shown by behavioural studies specifically tailored for studying addictive-like behaviour (1, 2). The rewarding and incentive effects of alcohol and others addictive substances, result from their capability to enhance mesolimbic dopamine (DA) transmission, as well as to affect the cannabinoid system, which is able to fine-tune the activity of DA neurons (3). ACD directly increases DA neurotransmission (4), but the neural underpinning the operant behaviour for oral-self administered ACD still remains poorly understood. Since D2 and CB1 receptors are involved in alcohol addiction (3), as well as their interplay (5), in thus study we aimed at investigating their contribution in ACD operant behaviour, able to capture the key aspects of addictive-like behaviour, such as the acquisition and maintenance during training, drug-seeking during extinction, and relapse after a-week deprivation. In doing so, we took advantage from the administration of a D2 receptor agonist, quinpirole (0.03mg/kg, i.p.), and a CB1 receptor antagonist, AM281 (1 mg/kg, i.p.), both administered during extinction and relapse sessions. Our results show that oral ACD readily induced the acquisition and maintenance of an operant self-administration paradigm, and sustained a reinstatement behaviour. Quinpirole was able to significantly decrease the number of lever presses for ACD during extinction (p<0.05), and ACD intake during relapse (p<0.01; p<0.001). AM281 administration showed a similar reduction in the number of lever presses for ACD during extinction (p<0.05) and relapse sessions (p<0.05; p<0.001). Oral ACD elicits clear motivational properties, and displays addictive-like features, which are modulated by D2 and CB1 signalling, receptors involved in impulsivity and addiction development (6, 7). These findings further strengthen the mandatory need for taking into account ACD's crucial role in ethanol-related behaviors. 1. Rodd-Henricks Z.A., Melendez R.I., Zaffaroni A., Goldstein A., McBride W.J. and Li T.K. (2002) Pharmacol Biochem Behav. 2. 72(1-2):55-64; 2. Cacace S., Plescia F., Barberi I. and Cannizzaro C. (2012) Alcohol Clin Exp Res. 36(7):1278-87; 3. Vengeliene V., Bilbao A., Molander A. and Spanagel R. (2008) Br J Pharmacol. 154(2):299-315; 4. Melis M., Enrico P., Peana A.T. and Diana M. (2007) Eur J Neurosci. 26(10):2824-33 5. Fitzgerald M.L., Shobin E. and Pickel V.M. (2012) Prog Neuropsychopharmacol Biol Psychiatry. 38(1):21-9; 6. Trifilieff P. and Martinez D. (2013) Neuropharmacology http://dx.doi.org/10.1016/j.neuropharm.2013.06.031 [Epub ahead of 8. print]; 7. Sidhpura N. and Parsons L.H. (2011) Neuropharmacology 61(7):1070-87.