Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task: Pharmacological Studies and the Role of Individual Differences

Patrick A. Randall, Marta Pardo, Eric J. Nunes, Laura López Cruz, V. Kiran Vemuri, Alex Makriyannis, Younis Baqi, Christa E. Müller, Mercè Correa, John D. Salamone

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D2 antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A2A antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

Original languageEnglish (US)
Article numbere47934
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 22 2012

Fingerprint

Choice Behavior
choice feeding
dopamine
Individuality
Modulation
Pharmacology
Rats
Dopamine
Food
haloperidol
Signal transduction
rats
Haloperidol
signal transduction
antagonists
Signal Transduction
appetite suppressants
Drug therapy
cannabinoids
Appetite Depressants

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Randall, Patrick A. ; Pardo, Marta ; Nunes, Eric J. ; López Cruz, Laura ; Vemuri, V. Kiran ; Makriyannis, Alex ; Baqi, Younis ; Müller, Christa E. ; Correa, Mercè ; Salamone, John D. / Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task : Pharmacological Studies and the Role of Individual Differences. In: PloS one. 2012 ; Vol. 7, No. 10.
@article{a40889f266f54edb8c9ca98bd8ba57ac,
title = "Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task: Pharmacological Studies and the Role of Individual Differences",
abstract = "Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D2 antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A2A antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.",
author = "Randall, {Patrick A.} and Marta Pardo and Nunes, {Eric J.} and {L{\'o}pez Cruz}, Laura and Vemuri, {V. Kiran} and Alex Makriyannis and Younis Baqi and M{\"u}ller, {Christa E.} and Merc{\`e} Correa and Salamone, {John D.}",
year = "2012",
month = "10",
day = "22",
doi = "10.1371/journal.pone.0047934",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task : Pharmacological Studies and the Role of Individual Differences. / Randall, Patrick A.; Pardo, Marta; Nunes, Eric J.; López Cruz, Laura; Vemuri, V. Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E.; Correa, Mercè; Salamone, John D.

In: PloS one, Vol. 7, No. 10, e47934, 22.10.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dopaminergic Modulation of Effort-Related Choice Behavior as Assessed by a Progressive Ratio Chow Feeding Choice Task

T2 - Pharmacological Studies and the Role of Individual Differences

AU - Randall, Patrick A.

AU - Pardo, Marta

AU - Nunes, Eric J.

AU - López Cruz, Laura

AU - Vemuri, V. Kiran

AU - Makriyannis, Alex

AU - Baqi, Younis

AU - Müller, Christa E.

AU - Correa, Mercè

AU - Salamone, John D.

PY - 2012/10/22

Y1 - 2012/10/22

N2 - Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D2 antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A2A antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

AB - Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D2 antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A2A antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

UR - http://www.scopus.com/inward/record.url?scp=84867708978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867708978&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0047934

DO - 10.1371/journal.pone.0047934

M3 - Article

C2 - 23110135

AN - SCOPUS:84867708978

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e47934

ER -