Central versus peripheral mechanisms in discriminative response control by d-amphetamine and related compounds

To investigate the role of central vs. peripheral mechanisms in discriminative response control by pharmacological agents, the present study compared acquisition of a two-lever choice discrimination by three groups of albino rats required to discriminate either d-amphetamine sulfate (0.8 mg/kg), 1-amphetamine sulfate (0.8 mg/kg) or para-hydroxyamphetamine hydrobromide (1.01 mg/kg) from saline. The drug condition was paired with reinforcement on one lever and the nondrug condition with the opposite lever for Ss in each group during training. The measure of response control was the proportion of cue appropriate responses during ten-minute extinction tests interspersed at four-day intervals during acquisition. Following acquisition, the administration of phentolamine hydrochloride (10 mg/kg) prior to drug injections was investigated to determine the relative importance of peripheral cues in these drug controlled discriminations. The results of acquisition data clearly indicate the importance of central activity in the control of responding by drugs. Superior control was exhibited by the d-amphetamine vs. saline group, intermediate performance was displayed by the 1-amphetamine vs. saline group and the para-hydroxy-amphetamine vs. saline group failed to acquire the discrimination. Pretreatment with phentolamine failed to produce meaningful results due to nonspecific behavioral effects of this agent.