The roles of specific dopamine (DA) receptors in the expression of various behavioral effects, including those induced by cocaine, are the subject of these investigations. Particular attention is focused on psychomotor stimulant and subjective interoceptive, and reinforcing effects. Several studies have indicated a role of DA in reinforcing effects of drugs and natural reinforcers such as food. A link between DA D2 receptors and obesity through a modification of brain reinforcement mechanisms has also been suggested. One hypothesis suggests that decreased expression of DA D2 receptors decreases the effectiveness of all reinforcers. Using behavioral economic measures we assessed the reinforcing effects of food in DA D2 receptor mutant mice. Behavioral economic theory shows that consumption of a commodity, or demand, is a function of price. Thus, rate of reinforcement (consumption of the commodity) was assessed as a function of the number of required responses (fixed-ratio value, or behavioral price of the commodity). The data were fitted with the equation: logQ=logQ0+k(e-Q0C-1), where C = the price of each reinforcer, k = the range of the data, is a free parameter representing the inverse of reinforcer efficacy, and Q0 is a free parameter representing consumption under no-price conditions, indicating the reinforcing efficacy of the commodity. The demand curve decreased more steeply after injection of the dopamine D2 receptor antagonist, eticlopride, consistent with our previous findings that Q0 is lower in DA D2 KO than HET or WT mice. This was most recently demonstrated using a rapid assessment procedure that will facilitate other experiments. Using traditional procedures the assessment of behavioral economic measures was excessively time consuming. In drug self-administration procedures catheter life is often so limited that these assessments cannot be made with traditional methods. Our rapid assessment procedure will allow application of behavioral economic measures to self-administration procedures where catheter life normally precludes their use. Dopaminergic mechanisms appear to be largely involved in attention deficit hyperactivity disorder (ADHD). In order to study these mechanisms and how they regulate attention a widely used laboratory analog of the continuous performance test (5-choice serial reaction time task or 5CSRTT) was implemented. Unfortunately, the effects of drugs that are useful in treating ADHD are not reliably active under this procedure. Reports from clinicians indicate that attention problems are more pronounced in individuals experiencing intermittent rather than continuous reinforcement. We modified the 5CSRTT so that correct responses were reinforced with a delay. Drugs that were and were not expected to enhance performance were then administered before experimental sessions. Significant increases in accuracy of signal detection were more robustly obtained when there was a delay in reinforcement with d-amphetamine and methylphenidate, but not morphine a drug inactive in ADHD. With improved predictive validity we can now use the 5CSRTT to study dopaminergic mechanisms in attention processes.

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National Institute on Drug Abuse
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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
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; 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