Eight White Carneau pigeons were trained to discriminate 1.0 or 1.7 mg/kg of cocaine from saline.A fixed number of consecutive key peck responses on one key after the administration of cocaine resulted in 4-s access to mixed grain.The same number of consecutive responses on the other key after saline also produced food.Different doses of cocaine and other drugs were tested to determine their ability to substitute (80% or more responding on the cocaine-appropriate key).The test drugs were selected to determine the selectivity of the cocaine discrimination in pigeons as well the role of different monoamines in mediating this behavioral effect.The drugs included other psychomotor stimulants, antidepressants, clonidine, yohimbine, other dopamine ((1-2-[bis(4-fluoro-phenyl)-methoxy]ethyl)4-3-phenylpropylpiperazine, GBR 12909) and serotonin (5-HT, sertraline) reuptake blockers, a D₁ (SKF 75670), D₂ (quinpirole), and 5-HT_1A (8-hydroxy-2-(di-n-propylamino)tetralin, 8-PH-DPAT) agonist as well as the 5-HT₃ antagonists, MDL 72222, LY 278584 and ondansetron.In addition, prazosin, an α₁ adrenergic antagonist, SCH 23390, a D₁ antagonist; raclopride, a D₂ antagonist and 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190), a putative 5-HT_1A antagonist, were given in combination with cocaine to determine their ability to block the discriminative stimulus (DS) effects of cocaine, i.e., reduce drug-appropriate responding to 20% or less.The psychomotor stimulants, d-amphetamine and d-methamphetamine, completely substituted for cocaine and were similar in potency to each other and cocaine.The antidepressants l-deprenyl, imipramine, tomoxetine and bupropion also occasioned cocaine-appropriate responding.However, only partial substitution was seen with fluoxetine, clonidine, GBR 12909, quinpirole, SKF 75670 and 8-OH-DPAT.Responding occurred primarily on the saline-appropriate key after the administration of yohimbine, sertraline and the 5-HT₃ antagonists.Prazosin, raclopride, SCH 23390 and NAN-190 blocked the DS effects of cocaine.Taken as a whole, these results indicate that the DS effects of cocaine are mediated not only by dopaminergic systems in the pigeon, as has been demonstrated in other species, but also at least in part by noradrenergic systems.Serotonin systems, in contrast, do not appear involved, although the results with fluoxetine, 8-OH-DPAT and NAN-190 warrant further investigation.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Preclinical	CN	Beijing Normal University	08 May 2017

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