Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation: evidence for the direct involvement of dopamine in brain reinforcement mechanisms.

A two-level intracranial self-stimulation (ICSS) paradigm was developed in which both rate-independent and dependent measures of ICSS could be obtained simultaneously. Responses at the first lever resulted in stimulation which decreased in magnitude after every fifth response, while responses at the second lever reset the current available. The current at which the reset responses occurred was defined as the 'reward threshold'. In addition, the rate of responding was determined at each current for which the animals responded during this stimulate-reset sequence. Decreased reward following treatment with the neuroleptic pimozide, a specific blocker of dopamine receptors, was demonstrated by an elevated 'reward threshold'. The same effect could be obtained in control animals by making each stimulation less rewarding, i.e., by decreasing the amount of charge per stimulation. Pimozide increased 'reward threshold' without a generalized disruption of response rates. While rates were decreased at low currents they were unchanged at high currents. 'Reward threshold' was decreased following D-amphetamine treatment, and was accompanied by a dose-related decrease in response rates at high to medium current intensities. These data suggest that neuroleptic attenuation of ICSS is due to diminished reward and not to motor deficits. Further, due to the specificity of pimozide, they suggest a direct role for dopamine in the mediation of reward.