A new view of the effect of dopamine receptor antagonism on operant performance for rewarding brain stimulation in the rat
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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.
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).
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.
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.
Like indirect dopamine agonists, pimozide does not alter the sensitivity of brain reward circuity but changes reward-system gain, subjective effort costs, and/or the value of activities that compete with ICSS. The 3D method is more sensitive and informative than the 2D methods employed previously.
KeywordsPimozide Opportunity cost Neuroeconomics Reward mountain Intracranial self-stimulation ICSS Neuroleptics
The research was supported by a grant to PS from the Canadian Institutes of Health Research (#MOP–74577), a group grant from the “Fonds de recherche Québec—santé” to the “Groupe de Recherche en Neurobiologie Comportementale”/Center for Studies in Behavioural Neurobiology (Shimon Amir, p.i.), support for PS from the Concordia University Research Chairs program, and scholarships to ITP from the “Consejo Nacional de Ciencia y Tecnologia” (CONACYT, #209314) and “le Ministère de l'Éducation, du Loisir et du Sport du Québec” (PBEEE-1M, #140498). David Munro built and maintained the computer-controlled equipment for experimental control and data acquisition. Software for experimental control and data acquisition was written and maintained by Steve Cabilio. The authors thank Brian Dunn for helpful comments on the manuscript.
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