Nisoxetine and amphetamine share discriminative stimulus properties in mice.
The interaction of amphetamine with noradrenergic neurons could mediate a portion of the drug's discriminative stimulus properties. To test this hypothesis, mice were trained to discriminate 1.0 or 3.2 mg/kg amphetamine, 32 mg/kg of the selective norepinephrine uptake inhibitor, nisoxetine, or 32 mg/kg nisoxetine + 1.0 mg/kg amphetamine from saline. Differential drug- or saline-appropriate responding was determined using a two photocell-beam procedure with beam interruption as the operant. Reinforcement (5-sec access to evaporated milk) was presented on a fixed-ratio 20 (FR-20) schedule. Mice trained to discriminate 1.0 mg/kg amphetamine from saline generalized to nisoxetine (32 mg/kg) alone and to doses of 0.56 mg/kg amphetamine and above but not to lower doses unless pretreated with nisoxetine (20 or 32 mg/kg). Mice trained to discriminate nisoxetine (32 mg/kg) from saline generalized to 0.56, 1.0 and 3.2 mg/kg amphetamine and generalized to all amphetamine doses when pretreated with nisoxetine (32 mg/kg). Mice trained to discriminate the drug combination from saline generalized to nisoxetine (32 mg/kg) alone, and to 3.2 mg/kg amphetamine tested alone, to 0.56 mg/kg of amphetamine or above when the lower dose of nisoxetine (20 mg/kg) was used, and to all test doses of amphetamine with nisoxetine (32 mg/kg) pretreatment. Mice trained to discriminate 3.2 mg/kg amphetamine from saline generalized to no test dose of amphetamine following either saline or nisoxetine (32 mg/kg) pretreatment. Testing with several doses of pentobarbital (1.0, 3.0, 10.0 and 18.0 mg/kg) resulted in saline-appropriate responding regardless of training group.(ABSTRACT TRUNCATED AT 250 WORDS)
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011292:Premedication; D011437:Propylamines / Q000494:pharmacology*; D013649:Taste
D011437:Propylamines; D005473:Fluoxetine; C011386:nisoxetine; D000661:Amphetamine