Cellular investigations of behavioral reinforcement.

Using the hippocampal-slice preparation, we attempted to demonstrate operant conditioning of pyramidal cell activity using local micropressure applications of transmitters and drugs as reinforcement; the same injections administered independently of bursting provided a control for direct pharmacological stimulation or facilitation of firing. The results suggested that the spontaneous bursting of individual CA1 pyramidal neurons may be reinforced with activity-contingent injections of dopamine and cocaine, whereas, CA3-bursting responses may be reinforced with contingently-applied dynorphin A. We sought to confirm these indications of cellular reinforcement at the behavioral level in studies of hippocampal self-administration (despite the fact that the hippocampus has been ignored as a brain site for chemical self-administration experiments). The results suggested that dynorphin A is a powerful reinforcer of hippocampal self-administration behavior when injected in the CA3 field; experiments still in progress suggest that dopamine can reinforce self-administration behavior when injected in the CA1 field. Successful prediction of new behavioral data from operant-conditioning data at the cellular level helps to validate the cellular data by providing suggestive evidence of interrelationship between cellular and behavioral operant conditioning processes.