Nucleus accumbens dopamine depletions alter relative response allocation in a T-maze cost/benefit task

doi:10.1016/0166-4328(95)00151-4

Behavioural Brain Research

Volume 74, Issues 1–2, January 1996, Pages 189-197

https://doi.org/10.1016/0166-4328(95)00151-4 Get rights and content

Abstract

This experiment was conducted to study the role of nucleus accumbens dopamine in the performance of a novel T-maze cost/benefit procedure. Rats were trained on a T-maze task for food reinforcement. Under one of the test conditions, one arm of the maze contained a high reinforcement density (4 × 45 mg Bioserve pellets) and the other arm contained a low reinforcement density (2 × 45 mg pellets). A large vertical barrier (44 cm) was placed in the arm that contained the high density of food reinforcement. In the second test condition, a separate group of rats was trained in the same T-maze, in which there were 4 food pellets in the arm that was obstructed by the barrier, yet there were no food pellets in the unobstructed arm. After training rats received intra-accumbens of injections 6-hydroxydopamine or ascorbate vehicle. Nucleus accumbens dopamine depletions substantially decreased the number of selections of the obstructed arm with the high reinforcement density when the unobstructed arm also contained 2 food pellets. Dopamine-depleted rats in this condition showed increased selection of the no-barrier arm as well as decreased entry into the arm that contained the barrier. These effects persisted throughout the 3 weeks of post-surgical testing. Nevertheless, when the unobstructed arm contained no food pellets, and the only way to obtain food was to climb the barrier, rats with nucleus accumbens dopamine depletions showed only a modest effect on selections of the obstructed arm, which recovered by the second week of testing. Dopamine-depleted rats that were tested with food in the unobstructed arm showed significantly fewer barrier crossings than dopamine-depleted rats that were tested with no food in the unobstructed arm. Thus, the present findings are not consistent with the notion that nucleus accumbens dopamine depletion rendered the animals unable to climb the barrier, or set an absolute ceiling on the number of barrier crossings the animals could perform. Instead, the present results indicate that nucleus accumbens dopamine depletions affected the relative allocation of barrier climbing responses if alternative food sources were available.

References (69)

W. Bowers et al.
Differential effects of pimozide on response-rate and choice accuracy in a self-stimulation paradigm in mice
Pharmacol. Biochem. Behav.
(1985)
M.A. Bozarth et al.
Involvement of the ventral tegmental dopamine system in opioid and psychomotor stimulant reinforcement
Life Sci.
(1981)
M.S. Cousins et al.
Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat
Pharmacol. Biochem. Behav.
(1993)
K.N. Gannon et al.
Effects of procurement cost on food consumption in rats
Physiol. Behav.
(1983)
L. Hernandez et al.
Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis
Life Sci.
(1988)
L.W. Kaufman
Foraging costs and meal patterns in ferrets
Physiol. Behav.
(1980)
L.W. Kaufman et al.
Cost and meal patterns in wild -caught rats
Physiol. Behav.
(1983)
P.H. Kelly et al.
Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum
Brain Res.
(1975)
E.A. Kiyatkin et al.
Electrochemical monitoring of extracellular dopamine in nucleus accumbens of rats lever-pressing for food
Brain Res.
(1994)
L.D. McCullough et al.
The role of nucleus accumbens dopamine in responding on a continuous reinforcement operant schedule: A neurochemical and behavioral study
Pharmacol. Biochem. Behav.
(1993)

L.D. McCullough et al.

Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: A microdialysis and behavioral study

Brain Res.

(1992)

L.D. McCullough et al.

Increases in extracellular dopamine levels and locomotor activity after direct infusion of phencyclidine into the nucleus accumbens

Brain Res.

(1992)

J.B. Mitchell et al.

Opioid modulation and sensitization of dopamine release elicited by sexually relevant stimuli: A high speed chronoamperometric study in freely behaving rats

Brain Res.

(1991)

G. Mogenson et al.

From motivation to action: Functional interface between the limbic system and the motor system

Prog. Neurobiol.

(1980)

T.W. Robbins et al.

Limbic-striatal interactions in reward-related processes

Neurosci. and Biobehav. Rev.

(1989)

J.D. Salamone

The involvement of nucleus accumbens dopamine in appetitive and aversive motivation

Behav. Brain Res.

(1994)

J.D. Salamone et al.

Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure

Behav. Brain Res.

(1994)

J.D. Salamone et al.

Nucleus accumbens dopamine release increases during instrumental lever pressing for food but not free food consumption

Pharmacol. Biochem. Behav.

(1994)

J.D. Salamone et al.

The role of dopamine in response initiation: Effects of haloperidol and regionally-specific dopamine depletions on the local rate of instrumental responding

Brain Res.

(1993)

J.D. Salamone et al.

Ventrolateral striatal dopamine depletions impair feeding and food handling in rats

Pharmacol. Biochem. Behav.

(1993)

J.D. Salamone et al.

Characterization of the impaired feeding behavior in rats given haloperidol or dopamine-depleting brain lesions

Neuroscience

(1990)

R.E. Steinpreis et al.

The role of nucleus accumbens dopamine in the neurochemical and behavioral effects of phencyclidine: A microdialysis and behavioral study

Brain Res.

(1993)

P. Winn et al.

Comparative effects of infusions of hydroxydopamine into nucleus accumbens and anterolateral hypo thalamus induced by 6-hydroxydopamine on the response to dopamine agonists, body weight, locomotor activity and measures of exploration in the rat

Neuropharmacology

(1985)

J. Allison

Economics and operant conditioning

V.P. Bakshi et al.

Dopaminergic regulation of feeding behavior: I. Differential effects of haloperidol microinjection in three striatal subregions

Psychobiology

(1991)

D. Bindra

How adaptive behavior is produced: A perceptual -motivational alternative to response-reinforcement

Behav. Brain Sci.

(1978)

C.N. Cofer et al.

Motivation: Theory and Research

(1964)

Cousins, M.S. and Salamone, J.D., Nucleus accumbens dopamine depletions in rats affect relative response allocation in...

M.S. Cousins et al.

Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: Effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs

Psychopharmacology

(1994)

G. Di Chiara et al.

Preferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol and barbiturates: studies with transcerebral dialysis in freely moving rats

Ann. NY. Acad. Sci.

(1986)

A. Ettenberg et al.

Response artifact in the measurement of neuroleptic-induced anhedonia

Science

(1981)

J.L. Evenden et al.

Dissociable effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on choice and rate measures of reinforcement in the rat

Psychopharmacology

(1983)

H.C. Fibiger et al.

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward

Psychopharmacology

(1976)

S.C. Fowler et al.

Effects of haloperidol on the biophysical characteristics of operant responding: Implications for motor and reinforcement processes

Pharmacol. Biochem. Behav.

(1976)

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Research reportNucleus accumbens dopamine depletions alter relative response allocation in a T-maze cost/benefit task

Abstract

Pharmacol. Biochem. Behav.

Life Sci.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Life Sci.

Physiol. Behav.

Physiol. Behav.

Brain Res.

Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Brain Res.

Brain Res.

Prog. Neurobiol.

Neurosci. and Biobehav. Rev.

Behav. Brain Res.

Behav. Brain Res.

Pharmacol. Biochem. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Neuroscience

Brain Res.

Neuropharmacology

Economics and operant conditioning

Dopaminergic regulation of feeding behavior: I. Differential effects of haloperidol microinjection in three striatal subregions

Psychobiology

How adaptive behavior is produced: A perceptual -motivational alternative to response-reinforcement

Behav. Brain Sci.

Motivation: Theory and Research

Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: Effects of dopamine antagonist, cholinomimetic, sedative and stimulant drugs

Psychopharmacology

Preferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol and barbiturates: studies with transcerebral dialysis in freely moving rats

Ann. NY. Acad. Sci.

Response artifact in the measurement of neuroleptic-induced anhedonia

Science

Dissociable effects of d-amphetamine, chlordiazepoxide and alpha-flupenthixol on choice and rate measures of reinforcement in the rat

Psychopharmacology

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward

Psychopharmacology

Effects of haloperidol on the biophysical characteristics of operant responding: Implications for motor and reinforcement processes

Pharmacol. Biochem. Behav.

Research report
Nucleus accumbens dopamine depletions alter relative response allocation in a T-maze cost/benefit task