Several previous studies, including some from this laboratory, have shown that dopamine (DA) D2 receptors (D2Rs) are involved in the reinforcing effectiveness of different magnitudes of food reinforcement. We used a behavioral-economic model (Hursh and Silberberg, Psychol Rev. XX: XXX, 20xx) to quantify reinforcer effectiveness with food pellets as the commodity obtained and the required number of responses (FR schedule value) as price of the commodity. Demand functions relating consumption of the commodity to price were fitted to an exponential model with the equation logQ=logQ0+k(e(-Q0C)-1), where alpha represents decline rate of the curve and is inversely related to reinforcer effectiveness, Q represents the number of reinforcers consumed, Q0 represents maximum consumption at zero price, C represents the cost of each reinforcer (i.e. FR value), and k is the y-axis range of the function. Genetically engineered mice were studied in groups having deletions (knockout, KO, mice) of the three D2-like dopamine receptor subtypes (D2R, D3R, or D4R KO mice) and compared to their wild-type littermates. These subjects were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. As price increased, food consumption decreased, and did so more rapidly in DA D2R KO mice compared to WT littermates. This difference between KO and WT mice was obtained with both open and closed economies. No differences in demand for food reinforcement rate were obtained in D3R KO mice and WT littermates in either economic environment. With DA D4R KO mice the decreases in demand occurred at lower prices than with WT mice. However, this difference was only obtained in an open economy. In a closed there were no differences between DA D4R KO and WT mice. Because an assessment of demand may be influenced by how rapidly responding extinguishes due to a decrease in rate of reinforcement, the extinction of responding was studied in two different contexts. In one, food deliveries were entirely eliminated whereas in the other only the contingency between food deliveries and responses was eliminated by delivering food independently of responding. In both contexts a hyperbolic model of the form R=1/(1+kt), was fitted to the decreases in response rates during extinction. In that model R represents the response rate as a proportion of control, t represents session number (time in extinction), and k represents the decay parameter, which reflects rate of change (i.e., how quickly the behavior extinguishes). The model fit the extinction curves better when food was entirely eliminated than when food was delivered independently of responding, possibly due to the adventitious reinforcement for occasional responses with the response-independent food deliveries. Extinction occurred more rapidly in DA D2R KO mice compared to WT control mice in either context, indicating that the change in demand curves DA D2R KO mice was not secondary to a difference in extinction or perseverative responding. Extinction of responding was not different in KO compared to WT mice for either DA D3R or D4Rs in either context. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food. The results also suggest a role for the DA D2 receptor in the perseverance of behavior in the absence of reinforcement.

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Project End
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Budget End
Support Year
27
Fiscal Year
2016
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National Institute on Drug Abuse
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Soto, Paul L; Hiranita, Takato; Xu, Ming et al. (2016) Dopamine D?-Like Receptors and Behavioral Economics of Food Reinforcement. Neuropsychopharmacology 41:971-8
Soto, Paul L; Grandy, David K; Hursh, Steven R et al. (2015) Erratum to: behavioral economics of food reinforcement and the effects of prefeeding, extinction, and eticlopride in dopamine D? receptor mutant mice. Psychopharmacology (Berl) 232:1669
Soto, Paul L; Hiranita, Takato; Grandy, David K et al. (2014) Choice for response alternatives differing in reinforcement frequency in dopamine D2 receptor mutant and Swiss-Webster mice. Psychopharmacology (Berl) 231:3169-77
Soto, Paul L; Katz, Jonathan L (2013) Interactions of cocaine with dopamine D?-like antagonists in squirrel monkeys. Psychopharmacology (Berl) 226:393-400
Hutchinson, M R; Northcutt, A L; Hiranita, T et al. (2012) Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci 32:11187-200
Katz, Jonathan L; Su, Tsung-Ping; Hiranita, Takato et al. (2011) A Role for Sigma Receptors in Stimulant Self Administration and Addiction. Pharmaceuticals (Basel) 4:880-914
Soto, Paul L; Grandy, David K; Hursh, Steven R et al. (2011) Behavioral economics of food reinforcement and the effects of prefeeding, extinction, and eticlopride in dopamine D2 receptor mutant mice. Psychopharmacology (Berl) 215:775-84
Koffarnus, Mikhail N; Katz, Jonathan L (2011) Response requirement and increases in accuracy produced by stimulant drugs in a 5-choice serial reaction-time task in rats. Psychopharmacology (Berl) 213:723-33
Li, Su-Min; Collins, Gregory T; Paul, Noel M et al. (2010) Yawning and locomotor behavior induced by dopamine receptor agonists in mice and rats. Behav Pharmacol 21:171-81
Soto, Paul L; Katz, Jonathan L (2009) Fluoxetine does not alter the ability of dopamine D(1)- and D(2)-like agonists to substitute for cocaine in squirrel monkeys. Pharmacol Biochem Behav 92:219-23

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