Role of dopamine in d-amphetamine-induced discriminative responding.

In two-lever operant chambers, rats were trained in a food-reinforced discrimination task. Reward was contingent upon correct lever choices to the induced differential cue conditions of d-amphetamine (0.8 mg/kg) or saline throughout training on a differential reinforcement of low response rate (DRL-15 sec) schedule. Upon acquisition of discriminative response control the animals were pretreated with various neurochemical agents. Pretreatment with atropine, phentolamine, propranolol, methysergide or cinanserin did not block production of d-amphetamine lever responding. Nicotine and oxotremorine did not produce the amphetamine-like cueing effect. However, pimozide blocked the ability of animals to discriminate d-amphetamine and L-DOPA, in combination with Ro 4-4602 with or without amantadine, generated amphetamine-like responses. These results indicate a role of dopamine in the production of the amphetamine state and from the failure of apomorphine to exhibit the stimulus property of d-amphetamine and the antagonism by alpha-methyltyrosine of the d-amphetamine responding it is further suggested that this amphetamine state is produced via the releasing of newly synthesized dopamine.