Pharmacological Modulation of Cannabinoid, Glutamate, and TRPV1 Receptors

The CB1 cannabinoid receptor antagonist SR141716A [5-(4-chloro-phenyl)−1-(2,4-dichlorophenyl)−4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (National Institute of Mental Health, USA), the positive allosteric modulator of mGlu₅ receptors CDPPB (3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide) (National Institute of Mental Health, USA), the vanilloid TRPV1 antagonist capsazepine (N-[2-(4-Chlorophenyl)ethyl]−1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamide) (Tocris) and the FAAH inhibitor URB597 (Cyclohexylcarbamic acid 3'-(Aminocarbonyl)-[1,1'-biphenyl]−3-yl ester) (Tocris) were dissolved in 5% Tween 80/5% polyethylene glycol/saline and given intraperitoneally (i.p.). CDPPB (0.75 mg/kg) or its vehicle were administered 30 min before testing; URB597 (0.1 mg/kg) or its vehicle were administered 2 hr before testing; SR141716A was administered 30 min before CDPPB or URB597 at a dose that did not induce effects by itself (1 mg/kg) in adult rats (Manduca et al., 2015 (link); Sciolino et al., 2011 (link)). capsazepine (5 mg/kg) was injected 30 min before CDPPB and URB597. Drug doses and pre-treatment intervals were based on the literature (Manduca et al., 2015 (link); Ratano et al., 2017 (link)) and on pilot experiments. Solutions were freshly prepared on the day of the experiment and were administered in a volume of 1 ml/kg.