Am J Physiol Regul Integr Comp Physiol 286: R31–R37, 2004.
First published August 21, 2003; 10.1152/ajpregu.00282.2003.

Oral sucrose stimulation increases accumbens dopamine in the rat
Andras Hajnal,1 Gerard P. Smith,2 and Ralph Norgren1
1

Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine,
Hershey, Pennsylvania 17033; and 2Bourne Behavioral Research Laboratory, Weill Medical
College of Cornell University, New York-Presbyterian Hospital, White Plains, New York 10605
Submitted 22 May 2003; accepted in final form 20 August 2003

orosensory positive feedback; control of food intake; motivation
ALTHOUGH SUBSTANTIAL PROGRESS has been made in understanding the neural code for the sensory properties of gustatory
stimuli, much less is known about the neural basis for thehedonic qualities elicited by the same chemicals. For taste andbehavioral studies, sucrose is commonly used as an exemplar
of a palatable tastant because it is innately preferred by bothhumans and rodents (28, 33, 44, 59). In brief exposure tests,
preference increases as a monotonic function of concentration(19, 67). Sham-feeding studies in rats demonstrate that theorosensory stimulating effect of sucrose is sufficient to initiate
and maintain ingestion also in a concentration-dependent manner (25, 44, 63, 74). Human nutrition studies also reveal astrong effect of sweet tastants on regulation of hunger andsatiety (15, 18, 26, 37, 42, 43).
Considerable evidence implicates the mesencephalic dopamine (DA) system in motivational and reward processes (9, 21,
35, 40, 53, 75). Although its exact role remains controversial(10, 21, 35, 40), in the rat both natural and nonnatural (i.e.,
drug of abuse) rewards activate DA neurons in the ventral
tegmental area (VTA; A10) that project to the ventral striatum,
predominantly to the medial shell of the nucleus accumbens(NAcc) (11, 70). The evidence for the involvement of DA
systems in sucrose reward derives from studies that demon-

Address for reprint requests and other correspondence: A. Hajnal, Dept. of
Neural and Behavioral Sciences H181, Coll. of Medicine, Pennsylvania State
Univ., Hershey, PA 17033 (E-mail: ahajnal@psu.edu).
http://www.ajpregu.org

strate a suppression of both real and sham feeding by systemically applied DA antagonists (22, 25, 34, 56, 57, 66). Conversely, manipulations that increase DA levels also enhance
preference for and real intake of sucrose (12, 29, 62, 69).
Sham-feeding studies also have investigated the potency ofsugar solutions to alter forebrain DA systems (65, 73), but none
has directly assessed extracellular DA in the NAcc.
Microdialysis experiments demonstrated that intraorally applied saccharin causes an increase in extracellular levels ofNAcc DA in naive rats (Ref. 41; A. Hajnal, unpublished data).
In a previous experiment (29), we used chronic microdialysis
to demonstrate that a single sucrose concentration (0.3 M)
increased NAcc DA in experienced real-feeding rats. These
results eliminated the problems associated with in vitro neurochemistry but left open the specific contribution of pre- andpostabsorptive components of the ingested sucrose. Therefore,
in the present experiments, a gastric fistula preparation wasused to assess the role of orosensory factors alone in NAcc DA
activation. In the first experiment, ad libitum-fed rats were
given unrestricted access to different concentrations of sucrose
solutions during daily 20-min sham feeding and microdialysis
sessions. After the main effect was proven, we repeated thestudy in an additional group of rats with a similar protocol but
clamped the intake of sucrose to control for the differential
ingestion normally driven as a function of concentration.
Results from subsets of these data have appeared as abstracts(31, 32).
METHODS

Subjects and surgeries. Nineteen adult male Sprague-Dawley rats
(275–325 g, Charles River, Wilmington, MA) were housed individuallyon a 12:12-h light-dark schedule (lights on 7 AM) and kept on a standard
laboratory diet [Rodent Diet (W)8604; Harlan Teklad, Madison, WI]. For
implantation of microdialysis cannulas, the subjects were anesthetizedwith pentobarbital sodium (50 mg/kg ip) after a pretreatment withatropine sulfate (0.15 mg/kg ip). The rats were implanted stereotaxicallywith bilateral, 21-gauge stainless steel guide cannulas positioned above
the posterior medial NAcc (A 1.0 mm, L 1.0 mm from the bregma, andV 4.0 from the surface of the skull; Ref. 48).
After 1-wk recovery, the rats were deprived of food for 18 h andanesthetized as before to implant stainless steel gastric cannulas.
Cannula design and implantation surgery are described in detailelsewhere (64). The rats recovered for at least 14 days before the startof sham-feeding training.
All the procedures used in this experiment were approved by theInstitutional Animal Care and Use Committee of the Pennsylvania
State University College of Medicine and comply with the American
Physiological Society’s “Guiding Principles for Research Involving
Animals and Human Beings.”
The costs of publication of this article were defrayed in part by the paymentof page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

0363-6119/04 $5.00 Copyright © 2004 the American Physiological Society

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Hajnal, Andras, Gerard P. Smith, and Ralph Norgren. Oralsucrose stimulation increases accumbens dopamine in the rat. Am J
Physiol Regul Integr Comp Physiol 286: R31–R37, 2004. First published August 21, 2003; 10.1152/ajpregu.00282.2003.—Althoughtaste can influence meal size and body weight, the neural substrate forthese effects remains obscure. Dopamine, particularly in the nucleus
accumbens, has been implicated in both natural and nonnatural rewards. To isolate the orosensory effects of taste from possible postingestive consequences, we investigated the quantitative relationshipbetween sham feeding of sucrose and extracellular dopamine in the
nucleus accumbens with microdialysis in rats. Sucrose intake linearly
increased as a function of concentration (0.03 M, 18.07 ! 2.41 ml; 0.1
M, 30.92 ! 2.60 ml; 0.3 M, 43.28 ! 2.88 ml). Sham feeding also
stimulated accumbens dopamine overflow as a function of sucrose
solution concentration (0.03 M, 120.76 ! 2.6%; 0.1 M, 140.28 !
7.8%; 0.3 M, 146.27 ! 5.05%). A second experiment used the same
protocol but clamped the amount of sucrose ingested and revealed asimilar, concentration-dependent dopamine activation in the nucleus
accumbens. This is the first demonstration of a quantitative relationship between the concentration-dependent rewarding effect of orosensory stimulation by sucrose during eating and the overflow of dopamine in the nucleus accumbens. This finding provides new and strong
support for accumbens dopamine in the rewarding effect of sucrose.

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SUCROSE SHAM FEEDING AND ACCUMBENS DOPAMINE

Once separated, the compounds were measured with a Coulochem II
system (ESA; analytic cell: model 5014B, electrode 1 &175 mV,electrode 2 '175 mV; guard cell: model 5020, '300 mV). For oursystem, the detection limit for DA is "2.0 fmol/15 $l standard
sample. In brain microdialysates, DOPAC levels typically are (100fold higher than DA, so detection limits are not an issue.
Histology. Histology was performed to verify placement of the
microdialysis probes. The rats received an overdose of pentobarbital
sodium (150 mg/kg ip) and, once deeply anesthetized, were perfusedtranscardially with 0.9% saline solution followed by 10% formalin.
Blocks of the brains that included the NAcc were frozen and seriallysectioned at 50 $m. The sections were mounted on microscope slides,
stained with cresyl violet, and examined with a light microscope. Of
the 38 probes implanted in experiments 1 and 2, six failed to impingeon the target, the posterior shell of NAcc as defined in the Paxinos andWatson atlas (48). Data from these six cases were discarded.
Statistical analyses. Although both hemispheres were sampled, as
it happened, data were analyzed from only one probe in each rat. The
selection was made on the basis of the probe placement, the stabilityof the baseline samples, and the number of days (up to 3) that theprobe remained functional. On this basis, the final statistical analyses
included data for samples from 10 right and 9 left probes. DA dataobtained from the left and right hemispheres did not differ statistically[sample 4: F(1,55) # 0.829, P ) 0.37; n # 19].
Basal recovery of DA and DOPAC varied considerably between
subjects. For this reason, peak overflow of both molecules [area under
the peaks analyzed on a personal computer with a Chromatographic
Data System (ESA501)] was converted to a percentage of the meanvalues of three 20-min baseline samples taken during the hour before
the sham-feeding tests with the sucrose solutions. These percentage
data for DA and DOPAC were analyzed by separate two-way ANOVAs (sample % concentration) with repeated measures on the time
factor, i.e., 20-min samples, followed by post hoc Newman-Keuls
tests when justified (i.e., between samples across concentrations andtheir respective baseline). In addition, Wilks’ lambda test was used totest for the effects of a combination of dependent variables. Covariance and linear regression analyses were used for assessment of
dose-response curves and interactions. The 20-min fluid intakes wereanalyzed with one-way ANOVAs for the concentration effect andtwo-way ANOVAs for interactions between concentration % day ofpresentation. Statistical analysis was carried out with Statistica 6.0
software (Tulsa, OK), and differences were considered significant
when P ) 0.05.
RESULTS

Sham-fed intake of sucrose. During the first set of microdialysis tests, there was a significant effect of sucrose concentration on sham feeding [0.03 M, 18.07 ! 2.41 ml; 0.1 M,
30.92 ! 2.60; 0.3 M, 43.28 ! 2.88 ml; F(2,39) # 22.88, P )0.0001; Fig. 1] but no effect from the order of presentation[concentration % day of presentation: Wilks’ lambda # 0.91,
F(8,76) # 0.46, P # 0.87]. With one exception, the individual
concentration-response functions were positive, near linear,and highly correlated [r # 0.69, F(1,43) # 38.96, P ) 0.0001;
Fig. 2].
In experiment 2, all rats established stable sham-fed intake
of 0.03 M sucrose (19.80 ! 1.98 ml) with 3 days of training.
To fix the volume ingested while varying the concentration,
during microdialysis each rat was given 75% of its training
volume when it was tested with 0.03 M and 0.3 M sucrose. All
rats consumed all of this volume of both concentrations within
20 min.

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Training and tests for sham feeding with sucrose. The rats weremaintained on regular lab chow ad libitum, except for 1 h before and
1 h after the training and test sessions. A mild overnight water
deprivation (8 PM–10 AM) served to initiate licking during training
and, later on, to maintain the behavior when 0.03 M sucrose waspresented. Experience with real feeding reduces intake for three to fivetests during subsequent sham feeding (20, 74). Therefore, the rats inthe present experiments were naive to the postingestive effects ofsucrose; they never ingested sucrose with a closed gastric fistula.
Because of the limits of the microdialysis probes, each rat had only
three test days. Thus, to collect data for each concentration from eachrat, only three concentrations of sucrose were used (0.03, 0.1, and 0.3
M). These concentrations represent the dynamic range in the behavioral concentration-response function for sucrose in sham-feeding rats
(20). For the same reason (i.e., the failure of the microdialysis probes
after 3 days) and because a previous study failed to show DA
responses to water (29), water as a stimulus was omitted from thisstudy.
Throughout training, the different concentrations of sucrose were
presented randomly to minimize contrast effects (24, 27) or otherexpectancies (58). The rats were trained to sham feed each sucrose
solution at least three times before the microdialysis tests were
initiated. Training continued until the rats initiated sham feedingreliably and 20-min intakes were stable across test days. Thus training
lasted for 9–12 days before the tests in the microdialysis chambers.
Experiment 2 was designed to vary concentration while fixing thevolume of intake to control for the difference in the amount of
movement required to ingest volumes that ranged from "18 ml (0.03
M) to "43 ml (0.3 M). The same training protocol was used inexperiment 2 with the following modifications. 1) Before random
presentation of the three sucrose concentrations, the rats (n # 5) sham
fed the lowest concentration of sucrose (0.03 M) for 3 days toestablish a baseline intake for clamping volume. 2) From day 4 on
through the remaining training and the microdialysis tests, the rats
received the same volume of the two concentrations of sucrose. This
volume was 75% of the average intake of 0.03 M sucrose by each rat
on the last 2 days of the baseline period. This criterion was usedbecause pilot studies in a separate set of rats (n # 5) revealed that, atthe concentrations to be used at testing, rats would not necessarily
consume 100% of the 0.03 M sucrose volume but they did ingest 75%
consistently.
Microdialysis and HPLC. Microdialysis probes were constructedwith silica glass tubing (37-$m ID; Polymicro Technologies, Miami
Lakes, FL) inside a 26-gauge stainless steel tube with a tip of cellulose
tubing (20-kDa cutoff, 0.2-mm OD % 2-mm length; Spectrum, Ranch
Dominguez, CA). They were perfused through a microdialysis swivel(375/D/22QE; Instech Laboratories, Plymouth Meeting, PA) withartificial cerebrospinal fluid [aCSF; in mM: 145 NaCl, 2.7 KCl, 1.2
CaCl2, 1.0 MgCl2, and 2.0 Na2HPO4 in HPLC-grade water (Fisher
Scientific International, Pittsburgh, PA) adjusted to pH 7.4] at a rateof 1.0 $l/min with microsyringe pumps (model A99; Razel Scientific
Instruments, Stamford, CT). The outlet branch of the probe led to a
400-$l vial clipped to a flexible cable 15 cm above the head of the rat.
To reduce the oxidation of DA, the vials were prefilled with 5 $l of
aCSF solution containing 0.1 M HCl and 100 $M EDTA. Microdialysis was conducted in three sessions on each animal, one session perday. At least 12 h before the first test day, the bilateral microdialysis
probes were inserted. They extended 4.0 mm beyond the guide shafts
to reach the target area and were left implanted for all three test days.
DA and the monoamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were analyzed by reverse-phase HPLC withcoulometric detection. Samples (15 $l) were injected with an autosampler (ESA 540, Chelmsford, MA) to a 15-cm column with 3-mm
bore and 3-$m C-18 packing (ESA MD-150). The mobile phase
contained 60 mM sodium phosphate, 100 $M EDTA, 1.24 mM
heptanesulfonic acid (Sigma), and 6% (vol/vol) methanol at pH 3.6.

SUCROSE SHAM FEEDING AND ACCUMBENS DOPAMINE

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DA and DOPAC changes in response to sham-fed sucrose.
The basal amount of DA and DOPAC (mean ! SE) in the
dialysate was 34.8 ! 12.4 fmol/15 $l and 0.41 ! 0.1 pmol/15$l, respectively.
In experiment 1, extracellular DA in the NAcc increased in
response to sham-fed sucrose across all concentrations (0.03
M, 120.76 ! 2.6%; 0.1 M, 140.28 ! 7.8%; 0.3 M, 146.27 !
5.05%; sample 4 in Fig. 3, top). The concentration effect was
statistically significant [sample 4: F(2,39) # 6.5725, P )0.01], as was its positive linear correlation [r # 0.407,
F(1,55) # 10.901, P ) 0.002]. Post hoc tests revealed that
whereas the effect of the lowest concentration (0.03 M) on DA
overflow was significantly different from that of the higher
concentrations (0.1 and 0.3 M; P # 0.008 and P # 0.003,

Fig. 2. Individual dose-response curves in sham-feeding sessions with different concentrations of sucrose. The volumes ingested in the 20-min shamfeeding sessions during microdialysis were normalized to the intake of thelowest concentration. Thin lines represent intakes from individual rats identified by log names (GF1–16). [Data from 2 rats (GF7, 12) were excluded fromthe analysis and from this article because of either misplacement or malfunction of the probes.] Thick line represents the mean (n # 14).

Fig. 3. Extracellular levels of dopamine (DA; top) and 3,4-dihydroxyphenylacetic acid (DOPAC; bottom) in the nucleus accumbens (NAcc) in response
to sham licking of sucrose in experiment 1. Values are expressed as % of meanbaseline (!SE; n # 14) before, during, and after 20 min of unrestricted sucrose
access (sucrose). Different concentrations were presented on consecutive days inthe same ad libitum-fed rats, in a counterbalanced fashion. Statistical symbols
indicate results of post hoc tests with significant differences from the baseline(sample 3: *P ) 0.01, #P ) 0.05). For further analyses see RESULTS.

respectively), there was no statistical difference between theeffect of 0.1 M and 0.3 M (P # 0.432).
Sham feeding all three concentrations of sucrose also increased DOPAC (Fig. 3, bottom). The increase began duringsucrose ingestion and lasted for at least 80 min when samplingceased. There was a dose effect [F(2,280) # 6.6160, P ) 0.02;
Fig. 3, bottom], which was a result of the strongest sucrose
concentration differing from the lower concentrations that were
statistically identical (post hoc tests: samples 5 and 6, P ) 0.02
and P ) 0.04, respectively).
In experiment 2, sham feeding of equal volumes of weak andstrong sucrose increased extracellular DA significantly overbaseline and the increase was greater for 0.3 M than for 0.03 M[F(1,71) # 28.66, P ) 0.02; sample 4: 156.05 ! 11.78% vs.
126.47 ! 2.83%; post hoc test, P ) 0.03; Fig. 4, top]. The
correlation between sucrose concentration and the DA response was statistically significant [r # 0.639, F(1,8) # 5.546,
P ) 0.05; Fig. 5]. Comparison for DOPAC also yielded astatistically significant concentration effect [F(1,71) # 13.79,
P ) 0.05; Fig. 4, bottom] carried by differences at 20 min after
the sham-feeding session (post hoc test: sample 5, P ) 0.02).
Histology. The tips of all probes that provided data werelocated in the caudomedial NAcc (A 10.0–10.6 according toRef. 48) medial to the anterior commissure (L 0.8–1.8). The
area from which samples were collected was reconstructedfrom individual probe placements and is depicted in Fig. 6. The
actual tracks of probe tips were often curved because of theflexibility of the membrane and gliosis in the surrounding brain
tissue. This feature and the extensive overlap of the probe sites

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Fig. 1. Intake of sham-fed sucrose in daily 20-min sessions at different
concentrations. Values are means (!SE) and include data from the microdialysis sessions. Asterisks depict intake of individual rats (in ml; n # 14). Flags
indicate overlapping data points. Intake in the microdialysis cages and in the
training cages did not differ statistically. For more details and statistics, see
RESULTS.

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SUCROSE SHAM FEEDING AND ACCUMBENS DOPAMINE

made a more precise analysis of individual sampling sites
impractical. Overall, the sampled brain region corresponded tothe midposterior aspect of the medial shell and medial core of
the NAcc.
DISCUSSION

Fig. 5. Correlation between DA release in the NAcc and concentration of
sucrose in experiments 1 and 2. Symbols depict individual data of peak DA
release expressed as % of the baseline (identical to sample 4 in Figs. 3, top, and4) across different concentrations of oral sucrose (0.03, 0.1, and 0.3 M inexperiment 1 and 0.03 and 0.3 M in experiment 2). Open circles: data fromexperiment 1, in which rats with open gastric fistula had unlimited access tosucrose. Half-filled triangles: data from experiment 2, in which rats sham fed
a restricted amount of sucrose. Dashed line: regression line for experiment 1.
Solid line: regression line for experiment 2. Numbers are the log numbers ofindividual rats in experiment 2. For further explanation and statistics, see
RESULTS.

Fig. 4. Extracellular levels of DA (top) and DOPAC (bottom) in the NAcc in
response to sham licking of sucrose in experiment 2. Values are expressed as% of mean baseline (!SE; n # 5) before, during, and after 20-min shamfeeding of the same volume of 0.03 M or 0.3 M sucrose. Statistical symbols
indicate results of post hoc tests with significant differences from the baseline(sample 3: *P ) 0.01, #P ) 0.05). For further analyses see RESULTS.

of sucrose intake by D1 and D2 DA receptor antagonists (34,57, 76).
The effects of the systemic antagonists and the reward
produced by sucrose are consistent with a dose-dependent
release of DA rather than with its tonic effect. Our prior study(29) using intra-accumbens reverse microdialysis of DA receptor antagonists revealed no tonic effect by D1 receptors on real
sucrose intake. When basal DA levels and sucrose intake wereincreased with nomifensine, however, the same blockade diddampen ingestion (29). Strong support for the importance ofphasic DA release comes from a recent in vivo voltametry
study demonstrating the specificity of DA transients in theaccumbens during cocaine administration (50).
Nonetheless, tonic DA levels remain relevant because they
regulate the phasic release of DA. Indeed, parallel experiments
in our laboratory (7, 8) revealed that experience with restrictedsucrose access may result in presynaptic neuroadaptation in theNAcc, including upregulation of the DA membrane transporterand downregulation of the D2/D3 autoreceptors, both factorsthat determine DA tone as well as the effectiveness of phasic
DA release. A further experiment illustrated the effects byshowing that experience with scheduled sucrose feeding resulted in augmented extracellular metabolite levels in response
to a subsequent chow (30). Because the rats in the present
experiment also had experience with the sucrose protocol
before the microdialysis sessions, the sustained high DOPAC
levels after the tests may also reflect altered tonic regulation.
Follow-up studies that control for contextual variables andfeeding conditions are needed to clarify the specificity andrelevance of this finding.

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Our present data reinforce previous findings showing thatrats sham feed sugar solutions in a concentration-dependent
manner (25, 44, 74). This observation underscores the role oforosensory factors in the preference of sucrose (“sweet reward”) without the confounding metabolic effects of ingested
food. The fundamental finding of our study was to demonstrate
a concentration-dependent increase in extracellular DA levelsin the NAcc. Moreover, the second experiment in which theintake volume was fixed substantially controlled for motor
activity. Although this finding (i.e., dose-response function of
accumbens DA to a rewarding stimulus) is unique, several
prior studies do support the observation. Previous behavioral
data showed a differential reinforcing effect of concentration
when small volumes of sucrose were consumed during operant
conditioning and other tasks (1, 72). Conversely, the reinforcing efficacy of sucrose concentration on progressive ratio
performance was dose-dependently suppressed by the DA
D2/D3 receptor antagonist raclopride (16). In contrast to ourexperiment, however, the small volumes used in these studies
minimized but did not eliminate postingestive feedback ofsucrose. Further support comes from pharmacological data in
sham-feeding studies that revealed a dose-dependent inhibition

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Fig. 6. Schematic frontal sections of the rat
brain’s left hemisphere showing microdialysis sites in the NAcc. Gray bars depict reconstructed extent of the active membrane of
the microdialysis probes (0.2 mm % 2 mm)
as identified in the histological analysis.
Black fields represent the areas of overlap
and, in turn, indicate the most often sampledbrain area. The number on each section is the
distance in millimeters anterior from thebregma according to Paxinos and Watson(48). Scale bar, 1 mm.

no detectable DA responses (29). In the present experiment, we
specifically presented the three different concentrations of
sucrose randomly during training to mitigate the chances ofhabituation or Pavlovian conditioning confounding the test
results (2–6, 21). Finally, the fact that the DA responses wereconcentration dependent further reduces the probability that a
conditioned response could account for a large proportion of
the phenomenon. Another observation was made contrary toprevious studies, in which a single preexposure to a complex
food stimulus reduced the DA response from the NAcc shell
during the second trial (3, 4, 6). Because of the extensive
training given to our rats, if any habituation took place, it
presumably was complete before our test trials. Thus the
responses that we measured after the training trials probably
reflected the direct sensory events. Another possible explanation for the lack of habituation is anatomic. Although DA
responses assayed in the NAcc shell show evidence of habituation, under similar circumstances those produced in the
NAcc core do not (2). Our probe placements were such that, onbalance, we probably measured some DA release from both
subdivisions.
Interestingly, the magnitude of the DA peaks in response to
sham licking the most preferred 0.3 M sucrose solution in thepresent experiment was significantly lower (i.e., 50–65%) thanthat of the DA responses to real feeding of the same concentration of sucrose in our previous experiments (29, 30). Thisdifference may reflect a contribution of postabsorptive factors.
Specifically, insulin has been proposed to influence DA function in the mesoaccumbens system (23, 52). Even in the
sham-feeding rat, an effect of preabsorptive insulin release on
the NAcc DA cannot be excluded.
In conclusion, the results demonstrate a significant, monotonic relationship between the intensity of orosensory stimulation provided by different concentrations of sucrose and theoverflow of DA from the nucleus accumbens. This relationshipwas caused by the oral concentration of sucrose because
postingestive effects were excluded by the use of sham feeding. This relationship was not caused by the amount of ingestive movements because it occurred when the volume ingested
was fixed. This is the first demonstration of such a quantitative
relationship with a natural food reward. It provides strong and

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How does oral sucrose affect accumbens DA? In fact, themesoaccumbens DA system has many potential connections
with the gustatory system. Palatable foods, including sucrose,
activate VTA neurons (47). Conversely, VTA lesions selectively reduce consumption of preferred sucrose solution (61).
The nucleus of the solitary tract (NST), the first central relay of
the gustatory system (45), possesses neural connections with
the VTA (36, 39). The NAcc also receives afferent projections
from the caudal NST (77) and communicates back to the NST(13, 68) via a circuit that includes the parabrachial nucleus(PBN) (71). The PBN, the second central gustatory relay,
projects to the gustatory cortex via the gustatory thalamus andalso projects heavily to limbic structures including the central
nucleus of the amygdala, the lateral hypothalamus, and the bed
nucleus of the stria terminalis (45), all of which send axons to
the NAcc shell (38) and are connected also to the VTA (46,51). The cortical gustatory area can also reach NAcc via
substantial connections to the central nucleus of the amygdala,
the lateral hypothalamus, and the prefrontal cortex (45, 60). In
summary, the anatomy suggests many avenues through which
gustatory neural activity in both the hindbrain and forebrain
could influence DA release in the terminal fields. Thus some ofthese neural substrates are very likely to be involved in behavioral activation by sucrose sham feeding.
Increases in NAcc DA, however, also occur in conjunction
with motor activity, reward learning, and the relative salienceof the stimulus driven by the deprivation state (3, 10, 14, 17,40, 49, 53–55). To control for these factors, we first used ratsthat received water instead of sucrose. In contrast to the present
experiment, overnight water deprivation failed to induce intake
comparable to that of the weakest concentration of sucrose. For
this reason, and also because of the limited number of microdialysis sessions possible in a given rat, water was omitted asa control from the present study. Nonetheless, in prior experiments using deprived rats with extensive training in 20-min
licking sessions, real water intake (i.e., nongastric fistula)failed to influence NAcc DA release (29, 30). This observationsuggests a dissociation of mechanisms that are responsible forincentive salience induced by need state and those that are
driven by the orosensory rewarding effects of sucrose (9).
As mentioned above, in a prior experiment that did include
water training in addition to sucrose, the control fluid produced

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SUCROSE SHAM FEEDING AND ACCUMBENS DOPAMINE

additional support for the importance of mesolimbic DA mechanisms in the motivating and rewarding effects of sweet taste.
ACKNOWLEDGMENTS
The authors thank W. D. Umbarger and N. Acharya for assistance with themicrodialysis and HPLC and K. Matyas and N. Horvath for histology.
GRANTSThis research was supported by National Institute of Deafness and Other
Communications Disorders Grants DC-04751 and DC-00240.
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