title: The role of dopamine D1 receptor transmission in effort-related choice behavior: Effects of D1 agonists.
abstract: Mesolimbic dopamine (DA), particularly in the nucleus accumbens, is a critical component of the brain circuitry involved in behavioral activation and effort-related processes. Although much is known about the characteristics of DA D2 receptor antagonism on effort-related choice behavior, less is known about the effects of D1 antagonism, and agonist/antagonist interactions. The highly selective D1 antagonist ecopipam was studied for its effects on effort-related choice behavior using the concurrent fixed ratio (FR) 5/chow feeding choice and T-maze barrier choice procedures. In rats tested on the FR5/chow feeding choice task, ecopipam shifted choice behavior, decreasing lever pressing for preferred high carbohydrate pellets but increasing consumption of lab chow. Also, ecopipam decreased selection of the high effort option (i.e., climbing the barrier to obtain a larger reward) in rats tested on the T-maze task, but did not disrupt arm preference or discrimination when no barrier was present. The D1 agonists SKF38393, SKF81297 and A77636 were assessed for their ability to reverse the effects of ecopipam, and in each case the D1 agonist significantly attenuated the effects of ecopipam, typically with an inverted-u shaped dose/response curve. SKF81297 also was able to reverse the effects of the catecholamine depleting agent tetrabenazine on T-maze performance. In summary, the present results implicate DA D1 receptors in the regulation of behavioral activation and effort-related functions, and demonstrate the utility of using tests of effort-related choice behavior for assessing the effects of D1 agonists.
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Yohn
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA; Department of Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Santerre
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA; Department of Psychiatry, Yale School of Medicine, 300 George ST., Suit 901, New Haven, CT 06511, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nunes
authors.affiliation: Pfizer Research Institute, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Rouba
authors.initials: R
authors.lastname: Kozak
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Podurgiel
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA; Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
authors.affiliation: Dept. of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. Electronic address: john.salamone@uconn.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D012055:Reinforcement Schedule; D012201:Reward; D013747:Tetrabenazine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D013747:Tetrabenazine
keywords: Anergia; Behavioral activation; D(1) receptor; Depression; Dopamine; Fatigue; Motivation; Nucleus accumbens