Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats.

Rationale: Motivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and rodents.

Objectives: Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats.

Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors.

People with depression and other neuropsychiatric disorders can experience motivational dysfunctions such as fatigue and anergia, which involve reduced exertion of effort in goal-directed activity. To model effort-related motivational dysfunction, effort-based choice tasks can be used, in which rats can select between obtaining a preferred reinforcer by high exertion of effort vs. a low effort/less preferred option.

Effort-related effects of chronic administration of the DA D receptor antagonist haloperidol via subcutaneous programmable minipumps: Reversal by co-administration of the adenosine A2A antagonist istradefylline.

Rationale: Long-acting antipsychotics such as haloperidol decanoate are becoming more commonly used. Long-acting depot formulations have several advantages, but secondary negative effects of prolonged delivery, including motivational dysfunctions, could have debilitating effects. Assessing the behavioral changes that emerge during chronic antipsychotic administration in rats could provide insight regarding the development of motivational dysfunctions and drug tolerance.

Effects of the atypical antipsychotic and D3/D2 dopamine partial agonist cariprazine on effort-based choice behavior: implications for modeling avolition.

Rationale: Cariprazine is an atypical antipsychotic that acts as a D3/D2 receptor partial agonist. In addition to treating positive symptoms of schizophrenia, cariprazine may have utility for treating negative symptoms. Rodent studies have focused on the effects of cariprazine on cognitive functions and behaviors thought to be related to anhedonia.

Effects of the dopamine depleting agent tetrabenazine on detailed temporal parameters of effort-related choice responding.

The dopamine-depleting agent tetrabenazine alters effort-based choice, suppressing food-reinforced behaviors with high response requirements, while increasing selection of low-cost options. In the present experiments, rats were tested on a concurrent fixed ratio 5/chow feeding choice task, in which high-carbohydrate Bio-serv pellets reinforced lever pressing and lab chow was concurrently available. Detailed timing of lever pressing was monitored with an event recording system, and the temporal characteristics of operant behavior seen after 1.

Complexities and paradoxes in understanding the role of dopamine in incentive motivation and instrumental action: Exertion of effort vs. anhedonia.

Instrumental behavior is a very complex and multifaceted process. Behavioral output during instrumental performance is influenced by a variety of factors, including associative conditioning, directional and activational aspects of motivation, affect, action selection and execution, and decision-making functions. Detailed assessments of instrumental behavior can focus on the temporal characteristics of instrumental behavior such as local frequency and response duration, and biophysical measures of response topography such as force output over time.