Abstract

RATIONALE:Previous studies of neuroleptic challenges to intracranial self-stimulation (ICSS) employed two-dimensional (2D) measurements (curve shifts). Results so obtained are ambiguous with regard to the stage of neural processing at which the drug produces its performance-altering effect. We substituted a three-dimensional (3D) method that measures reward-seeking as a function of both the strength and cost of reward. This method reveals whether changes in reward seeking are due to drug action prior to the output of the circuitry that performs spatiotemporal integration of the stimulation-induced neural activity.

OBJECTIVES:The aim of this study was to obtain new information about the stage of neural processing at which pimozide acts to alter pursuit of brain stimulation reward (BSR).

METHODS:Following treatment with pimozide (0.1 mg/kg) or its vehicle, the proportion of trial time allocated to working for BSR was measured as a function of pulse frequency and opportunity cost. A surface defined by Shizgal's reward-mountain model was fitted to the drug and vehicle data.

RESULTS:Pimozide lowered the cost required to decrease performance for a maximal BSR to half its maximal level but did not alter the pulse-frequency required to produce a reward of half-maximal intensity.

CONCLUSIONS:Like indirect dopamine agonists, pimozide does not alter the sensitivity of brain reward circuity but changes reward-system