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  • Discriminative stimulus effects of the novel imidazoline I₂ receptor ligand CR4056 in rats.

Discriminative stimulus effects of the novel imidazoline I₂ receptor ligand CR4056 in rats.

Scientific reports (2014-10-14)
Yanyan Qiu, Xiao-Hua He, Yanan Zhang, Jun-Xu Li
ABSTRACT

This study examined whether a novel imidazoline I₂ receptor ligand CR4056 could serve as a discriminative stimulus and whether it shares similar discriminative stimulus effects with other reported I₂ receptor ligands. Eight male Sprague-Dawley rats were trained to discriminate 10.0 mg/kg CR4056 (i.p.) from vehicle in a two-lever food-reinforced drug discrimination procedure. Once rats acquired the discrimination, substitution and combination studies were conducted to elucidate the underlying receptor mechanisms. All rats acquired CR4056 discrimination after an average of 26 training sessions. Several I₂ receptor ligands (phenyzoline, tracizoline, RS45041, and idazoxan, 3.2-75 mg/kg, i.p.) all occasioned > 80% CR4056-associated lever responding. Other drugs that occasioned partial or no CR4056-associated lever responding included methamphetamine, ketamine, the endogenous imidazoline ligand agmatine, the monoamine oxidase (MAO) inhibitor harmane, the α₂-adrenoceptor agonist clonidine, the μ-opioid receptor agonists morphine and methadone, and the selective I₂ receptor ligands BU224 and 2-BFI. The α₁ adrenoceptor antagonist WB4101, α₂ adrenoceptor antagonist yohimbine and μ-opioid receptor antagonist naltrexone failed to alter the stimulus effects of CR4056. Together, these results show that CR4056 can serve as a discriminative stimulus in rats, which demonstrates high pharmacological specificity and appears to be mediated by imidazoline I₂ receptors.

MATERIALS
Product Number
Brand
Product Description

Clonidine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Benzoylecgonine-d3 solution, 100 μg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Idazoxan hydrochloride
Sigma-Aldrich
Clonidine hydrochloride, solid
Sigma-Aldrich
Naltrexone hydrochloride
Sigma-Aldrich
Yohimbine hydrochloride, ≥98% (HPLC), powder
Supelco
Benzoylecgonine-d3 solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Yohimbine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Naltrexone hydrochloride, European Pharmacopoeia (EP) Reference Standard