THE DISCRIMINATIVE STIMULUS EFFECTS OF COCAINE IN PIGEONS

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 res ponses on one key after the administration of cocaine resulted in 4-se c access to mixed grain. The same number of consecutive responses on t he other key after saline also produced food. Different doses of cocai ne and other drugs were tested to determine their ability to substitut e (80% or more responding on the cocaine-appropriate key). The test dr ugs were selected to determine the selectivity of the cocaine discrimi nation in pigeons as well the role of different monoamines in mediatin g this behavioral effect. The drugs included other psychomotor stimula nts, antidepressants, clonidine, yohimbine, other dopamine is(4-fluoro -phenyl)-methoxylethyl)4-3-phenylpropyl piperazine, GBR 12909) and ser otonin (5-HT, sertraline) reuptake blockers, a D1 (SKF 75670), D2 (qui npirole), and 5-HT1A (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPA T) agonist as well as the 5-HT3 antagonists, MDL 72222, LY 278584 and ondansetron. In addition, prazosin, an alpha1 adrenergic antagonist, S CH 23390, a D1 antagonist; raclopride, a D2 antagonist and -methoxyphe nyl)-4-(2-phthalimmido)butyl]piperazine (NAN-190), a putative 5-HT1A a ntagonist, were given in combination with cocaine to determine their a bility to block the discriminative stimulus (DS) effects of cocaine, i .e., reduce drug-appropriate responding to 20% or less. The psychomoto r stimulants, d-amphetamine and d-methamphetamine, completely substitu ted for cocaine and were similar in potency to each other and cocaine. The antidepressants I-deprenyl, imipramine, tomoxetine and bupropion also occasioned cocaine-appropriate responding. However, only partial substitution was seen with fluoxetine, clonidine, GBR 12909, quinpirol e, SKF 75670 and 8-OH-DPAT. Responding occurred primarily on the salin e-appropriate key after the administration of yohimbine, sertraline an d the 5-HT3 antagonists. Prazosin, raclopride, SCH 23390 and NAN-190 b locked the DS effects of cocaine. Taken as a whole, these results indi cate that the DS effects of cocaine are mediated not only by dopaminer gic 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 fluoxe tine, 8-OH-DPAT and NAN-190 warrant further investigation.