The discriminative stimulus properties of nicotine, d-amphetamine and morphine in dopamine depleted rats.

Rats permanetly depleted of central dopamine (DA) via 6-OHDA neonatally were studied in relation to their ability to discriminate various psychoactive drugs from saline using a two-bar operant procedure. DA rats learned to discriminate both morphine (4 mg/kh) and d-amphetamine (0.9 mg/kg) as rapidly as controls and exhibited similar sensitivity when dose-generalization studies were conducted. However, DA rats appeared to tolerate higher doses of the same drug better than controls indicating that they were more tolerant to behavioral disruption. It was suggested that the behavioral disruption. It was suggested that the behavioral disruption usurons. DA rats had more difficulty learning to discriminate nicotine than controls. In fact the peripherally injected nicotine stimulus generalized to hippocampal (Hp) injections in controls but was not observed in DA rats. These data suggest that part of nicotine's discriminative stimulus properties may be contingent upon the integrity of a Hp-DA connection.