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摘要
Although imidazoline 12 receptor ligancls have been used as discriminative stimuli, the role of efficacy of 12 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I-2 receptor ligands B1J224 (a low-efficacy I-2 receptor ligand) and phenyzoline (a higher efficacy I-2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6 mg/kg B1J224 or 32 mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (B1J224) and 56 (phenyzoline) training sessions, respectively. B1J224 and phenyzoline completely substituted for one another symmetrically. Several 12 receptor ligancls (tracizoline, CR4056, RS45041, and idazoxan) all occasioned > 80% drug-associated lever responding in both discriminations. The 12 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned >80% drug-associated lever responding in rats discriminating 80224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D-2 receptor antagonist haloperidol and serotonin (5-HT)(2A) receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I-2 receptor ligand B1J224 shares similar discriminative stimulus effects with higher-efficacy I-2 receptor ligands such as phenyzoline and 2-BFI.
- 出版日期2015-2-15
