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The Novel cannabinoid antagonist SM-11 reduces hedonic aspect of food intake through a dopamine-dependent mechanism

Fois, Giulia R. and Fattore, Liana and Murineddu, Gabriele and Salis, Andrea and Pintore, Giorgio Antonio Mario and Asproni, Battistina and Pinna, Gérard Aimé and Diana, Marco (2016) The Novel cannabinoid antagonist SM-11 reduces hedonic aspect of food intake through a dopamine-dependent mechanism. Pharmacological Research, Vol. 113 (Part A), p. 108-115. ISSN 1043-6618. Article.

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DOI: 10.1016/j.phrs.2016.08.012

Abstract

Cannabinoids, endogenous and exogenously administered, are known to positively regulate food intake and energy balance. Since CB1 receptor antagonists reduce food intake and antagonize overweight, we developed a new CB1 receptor antagonist in an attempt to identify a compound with potential application in overeating disorders. The newly developed SM-11 compound dose-dependently decreases food intake in rats by 15–20%. Moreover, SM-11 reduces self-administration of palatable food in both food restricted and ad libitum fed rats, suggesting an action on the hedonic component of food intake. Thus, we next tested the effect of SM-11 on the stimulating properties of the CB1 receptor agonist WIN55,212-2 (WIN) on the electrophysiological activity of Nucleus Accumbens-projecting dopaminergic neurons of the ventral tegmental area (VTA). SM-11 fully and readily antagonized the WIN-induced increments in single spiking and burst firing of antidromically-identified dopamine neurons. When administered to naïve (no WIN-pretreated) rats, SM-11 did not alter basal neuronal activity, thereby suggesting a pure antagonistic profile. SM-11 thus appears as a promising candidate in the search of potential anti-obesity medications.

Item Type:Article
ID Code:11475
Status:Published
Refereed:Yes
Uncontrolled Keywords:Cannabinoid CB1 receptor antagonist, food intake, obesity, overweight, dopamine neurons, reward
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Area 05 - Scienze biologiche > BIO/15 Biologia farmaceutica
Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
Publisher:Academic Press / Elsevier
ISSN:1043-6618
Deposited On:20 Oct 2016 08:21

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