Differential involvement of dopamine in mediating the discriminative stimulus effects of low and high doses of caffeine in rats

The hypothesis that low and high doses of caffeine produce effects that are differentially mediated by dopamine (DA) receptor mechanisms was investiga ted in rats trained to discriminate either 10 or 56 mg/kg of caffeine from saline, Rats trained to discriminate 56 mg/kg of caffeine acquired the disc rimination in an average of 74 sessions, whereas rats trained to discrimina te 10 mg/kg of caffeine required an average of 108 sessions. The DA D-1 rec eptor agonist SKF 81297 and the DA D-2 receptor agonist R(-)-propylnorapomo rphine (NPA) generalized partially (50-75%) in rats trained to discriminate 10 mg/kg of caffeine, but produced predominantly saline-appropriate respon ding (< 40%) in rats trained to discriminate 56 mg/kg of caffeine. When SKF 81297 and NPA were combined, stimulus generalization was no greater than i t was when either agonist was tested alone, The DA uptake inhibitors cocain e and GBR 12909 produced predominantly saline-appropriate responding in bot h groups of rats. Neither the DA D-1 receptors antagonists SCH 23390 and SC H 31966, nor the DA D-2 receptor antagonists eticlopride and sulpiride, gen eralized in rats trained to discriminate 10 or 56 mg/kg of caffeine, When a dministered in combination with caffeine, both the DA D-1 and DA D-2 antago nists antagonized completely the discriminative stimulus effects of the low training dose of caffeine, but did not alter the discriminative stimulus e ffects of the high training dose. These results suggest that the discrimina tive stimulus effects of 10 mg/kg of caffeine, but not 56 mg/kg of caffeine , are dependent on, but not limited to, DA D-1 and D-2 receptor mechanisms. (C) 1999 Lippincott Williams & Wilkins.