Modeling operant behavior in the Parkinsonian rat

• Published in: Behavioural brain research 2009-03, Vol.198 (2), p.298-305
• Main Authors: Avila, Irene, Reilly, Mark P., Sanabria, Federico, Posadas-Sánchez, Diana, Chavez, Claudia L., Banerjee, Nikhil, Killeen, Peter, Castañeda, Eddie
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Behavioral psychophysiology; Biological and medical sciences; Conditioning, Operant; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine; Dopamine - deficiency; Fixed-ratio schedule; Food; Fundamental and applied biological sciences. Psychology; Male; Medical sciences; Memory; Memory, Short-Term; Microinjections; Motivation; Motor; Motor Activity; MPR; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Operant behavior; Organic mental disorders. Neuropsychology; Oxidopamine - administration & dosage; Oxidopamine - toxicity; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson Disease - psychology; Parkinson's disease; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Reinforcement, Psychology; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Sympatholytics - administration & dosage; Sympatholytics - toxicity; Time Factors
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2008.11.033

Mathematical principles of reinforcement (MPR; Killeen, 1994) is a quantitative model of operant behavior that contains three parameters representing motor capacity ( δ), motivation ( a), and short term memory ( λ). The present study applied MPR to characterize the effects of bilateral infusions of 6-OHDA into the substantia nigra pars compacta in the rat, a model of Parkinson's disease. Rats were trained to lever press under a 5-component fixed-ratio (5, 15, 30, 60, and 100) schedule of food reinforcement. Rats were tested for 15 days prior to dopamine lesions and again for 15 days post-lesion. To characterize functional loss relative to lesion size, rats were grouped according to the extent and the degree of lateralization of their dopamine loss. Response rates decreased as a function of dopamine depletion, primarily at intermediate ratios. MPR accounted for 98% of variance in pre- and post-lesion response rates. Consistent with reported disruptions in motor behavior induced by dopaminergic lesions, estimates of δ increased when dopamine was severely depleted. There was no support for different estimates of a based on pre- and post-lesion performance of any lesion group, suggesting that dopamine loss has negligible effects on incentive motivation. The present study demonstrates the usefulness of combining operant techniques with a theoretical model to better understand the effects of a neurochemical manipulation.