6‐Hydroxydopamine lesions of the nucleus accumbens attenuate the discriminative stimulus effects of d‐amphetamine

Abstract

AbstractTen rats were trained with a standard two‐lever procedure to discriminate d‐amphetamine (1.0 mg/kg i.p.) from saline. Training was continued until the rats emitted three or less responses on the incorrect lever before the first food presentation and more than 95% of the responses during a session occurred on the correct lever for five consecutive sessions.A descending range of doses from 1.0 to 0.17 mg/kg d‐amphetamine and saline were resulted to determine a drug‐dose generalization gradient including a threshold dose that resulted in drug‐appropriate responding. Following the determination of the threshold dose, the rats were lesioned with 6‐hydroxydopamine (6‐OHDA) or its vehicle. Three days were allowed for recovery from the lesion. The animals were then again tested starting with the threshold dose. A postlesion generalization gradient was then determined by testing the rats with increasing doses of the drug. Saline test sessions were randomly scheduled during the postlesion testing.The vehicle lesion produced a slight change in the generalization gradients. The 6‐OHDA lesion, however, resulted in a much larger attenuation in the discriminative stimulus function of the drug. Thus, it appears that destruction of the dopaminergic input into the accumbens only moderately alters the discriminative stimulus properties of d‐amphetamine.