Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats
Previous evidence demonstrated that drug-induced extracellular dopamine (DA) concentrations in the nucl. accumbens shell (AcbSh) might underlie different vulnerabilities to heroin addiction in inbred mice strains. We investigated a potential role of the responsiveness of the DA system in the AcbS...
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| Date: | 2015 |
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Інститут фізіології ім. О.О. Богомольця НАН України
2015
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| Cite this: | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats / Ch. Wang, H. Chen, X. Wang, R. Zhang, W. Hao // Нейрофизиология. — 2015. — Т. 47, № 3. — С. 255-261. — Бібліогр.: 23 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859984967610662912 |
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| author | Wang, Ch. Chen, H. Wang, X. Zhang, R. Hao, W. |
| author_facet | Wang, Ch. Chen, H. Wang, X. Zhang, R. Hao, W. |
| citation_txt | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats / Ch. Wang, H. Chen, X. Wang, R. Zhang, W. Hao // Нейрофизиология. — 2015. — Т. 47, № 3. — С. 255-261. — Бібліогр.: 23 назв. — англ. |
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| description | Previous evidence demonstrated that drug-induced extracellular dopamine (DA) concentrations
in the nucl. accumbens shell (AcbSh) might underlie different vulnerabilities to heroin
addiction in inbred mice strains. We investigated a potential role of the responsiveness of the
DA system in the AcbSh with respect to the vulnerability to heroin-influenced conditioned
place preference (CPP) in rats. Animals were randomly assigned to the heroin and saline
(control) groups. Heroin-group rats were then re-classified into two groups according to the
degree of heroin-induced CPP, high preference (HP) and low-preference (LP) ones. The levels
of extracellular DA and dihydroxyphenyl acetic acid (DOPAC) were estimated dynamically
by in vivo microdialysis. Compared with the saline group, extracellular DA and DOPAC
concentrations in the heroin-treated groups were significantly higher 30 min after the last
injection, but the DA level decreased sharply in these groups on days 1 and 3 and became
lower than that of the saline group. Compared with LP-group rats, HP-rats displayed a higher
heroin-induced increase in the DA concentration 30 min after the last heroin injection and
higher DOPAC and DOPAC/DA ratios 14 days after such injection. These results suggest
that differences in the DA system responsiveness in the AcbSh may determine individual
differences in vulnerability to heroin addiction.
Результати попередніх досліджень продемонстрували,
що змінений під впливом фармакологічних агентів
рівень дофаміну (DA) в шкаралупі nucl. accumbens
(AcbSh) є визначальним фактором для вразливості до
героїнової аддукції у лінійних мишей. Ми досліджували
можливу роль реактивності DA-ергічної системи AcbSh
у вразливості умовнорефлекторної преференції місця
(УРПМ) щодо героїну у щурів лінї Спрейг–Доулі.
Щури були рандомізовано поділені на «героїнову» та
контрольну групи. Щури першої з них потім додатково
поділи на дві групи відповідно до інтенсивності змін
УРПМ під впливом героїну – тварин з високою та низькою
«героїновою» преференцією (HP та LP). Рівні DA та
дигідроксифенілоцтової кислоти (DOPAC) у позаклітинному
просторі AcbSh оцінювали в динаміці за допомогою
мікродіалізу in vivo. Позаклітинні концентрації DА та
DOPAC у «героїнових» групах через 30 хв після останньої
ін’єкції були істотно вищими, ніж у контролі, але рівень DA
у тварин цих груп швидко знижувався і на першу та третю
добу ставав нижчим порівняно з контролем. Тварини групи
HP порівняно зі щурами групи LP демонстрували вищі
значення індукованого героїном збільшення концентрації
DA через 30 хв після останньої ін’єкції героїну та вищі
рівень DOPAC і відношення DOPAC/DA через 14 діб після
такої ін’єкції. Подібні результати дозволяють вважати, що
різниці в реактивності DA-ергічної системи в AcbSh можуть
визначати індивідуальні відмінності вразливості щодо
героїнової залежності.
|
| first_indexed | 2025-12-07T16:28:24Z |
| format | Article |
| fulltext |
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 3 255
UDC 612.826.4:663.991
Ch. WANG,1, 2 H. CHEN,2 X. WANG,2 R. ZHANG,1 and W. HAO1, 2
DOPAMINE RESPONSIVENESS IN THE NUCL. ACCUMBENS SHELL
AND PARAMETERS OF THE HEROIN-INFLUENCED CONDITIONED
PLACE PREFERENCE IN RATS
Received January 27, 2014
Previous evidence demonstrated that druginduced extracellular dopamine (DA) concentrations
in the nucl. accumbens shell (AcbSh) might underlie different vulnerabilities to heroin
addiction in inbred mice strains. We investigated a potential role of the responsiveness of the
DA system in the AcbSh with respect to the vulnerability to heroininfluenced conditioned
place preference (CPP) in rats. Animals were randomly assigned to the heroin and saline
(control) groups. Heroingroup rats were then reclassified into two groups according to the
degree of heroininduced CPP, high preference (HP) and lowpreference (LP) ones. The le vels
of extracellular DA and dihydroxyphenyl acetic acid (DOPAC) were estimated dyna mically
by in vivo microdialysis. Compared with the saline group, extracellular DA and DOPAC
concentrations in the herointreated groups were significantly higher 30 min after the last
injection, but the DA level decreased sharply in these groups on days 1 and 3 and became
lower than that of the saline group. Compared with LPgroup rats, HPrats displayed a higher
heroininduced increase in the DA concentration 30 min after the last heroin injection and
higher DOPAC and DOPAC/DA ratios 14 days after such injection. These results suggest
that differences in the DA system responsiveness in the AcbSh may determine individual
differences in vulnerability to heroin addiction.
Keywords: nucl. accumbens shell, heroin addiction, vulnerability, dopamine, conditioned
place preference (CPP).
1 Second Affiliated Hospital, Xinxiang Medical University, Xinxiang, China.
2Mental Health Institute, Second Xiangya Hospital, Central South University,
Changsha, China.
Correspondence should be addressed to W. Hao
(email: weihaocn@126.com).
INTRODUCTION
Individual vulnerability to the reinforcing effects of
drugs appears to be a crucial factor in the development
of addictions in humans. The mesolimbic dopamine
(DA) system has been implicated as an important
substrate for reinforcing effects of most drugs of abuse
[1] (like opioids, including heroin). The rewarding
effects of addictive drugs are thought to be mediated
by increased DAergic transmission in the projections
originating from the ventral tegmental area (VTA) that
innervate the nucl. accumbens (Acb) and prefrontal
cortex [2, 3].
Two subregions of the Acb, the dorsolateral core
and the ventromedial shell, are thought to subserve
different functions related to the reinforcing properties
of drug rewards. Some studies suggest that the Acb
shell (AcbSh) plays an important role in the reward
function of DA [4]. Rats can learn selfadministration
by perfusing DA uptake inhibitors (nomifensine [5] and
cocaine [6]) and also mixtures of D1 and D2 receptor
agonists [7] into the shell but not the core of the
above nucleus. In addition, systemic Damphetamine
influenced conditioned place preference (CPP), a
measure of reward, can be attenuated by selective
lesions of DAergic terminals in the AcbSh but not in
the core of this structure [8].
The link between DAergic functioning and
behavioral processes has been extensively studied
in the field of drug abuse [9]. The results allowed
researchers to suggest that individual differences in
the DAergic function can result in varying degrees of
susceptibility to drug abuse [10].
In animal studies, it has been argued that the
intrinsic properties of drugs of abuse do not account
per se for individual variability in the occurrence
of drug addiction, and different extracellular DA
concentrations in the AcbSh may underlie the above
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 47, № 3256
Ch. WANG, H. CHEN, X. WANG et al.
specificities [11]. Thus, individual differences in
the responsiveness of the DA system to novelty and
stress have been shown to predict the susceptibility of
individual animals to drug addiction [12]. According
to this hypothesis, individuals with a hyperresponsive
DA system would be more prone to drug addiction.
Furthermore, this difference in individual vulnerability
to addiction may be based on neural substrates and
genetic background [11].
Previous studies of addiction susceptibili ty
differences focused on different rat strains. Among
such different strains, dissimilar susceptibility to
addictive drugs, in particular amphetamine [13],
cocaine [14], alcohol [15], and opioids [16], has been
found, and the vulnerability difference was interrelated
with druginduced changes in the DA concentrations.
Some studies seem to suggest that highlyvulnerable
animals have a higher basal DOPAC/DA ratio in the
Acb and higher extracellular concentrations of DA in
this structure in response to the action of addictive
drugs [17, 18].
Conditioned place preference (CPP) is an evaluation
measure of the rewarding effect [19]. Rats of different
strains showed different intensities of druginduced
CPP, and it was suggested that genetic differences
may underlie dissimilar sensitivities to the place
conditioning procedure [20]. However, different CPP
dynamics can be seen in the same rat strains, which is
related to the response to novel environment. Animals
with high responses to novel environment tend to
have higher scores of the CPP development [21].
Nevertheless, it is not clear whether differences in the
CPP development and responses to novel environment
are also related to the DA responsiveness in the AcbSh
of rats of the same strain. Furthermore, there is a lack
of studies on the dynamic variety of extracellular DA
concentrations and DA update rate in the AcbSh the
samestrain rats, especially with respect to heroin
addiction.
In our study, we used brain microdialysis in freely
moving rats to examine the effect of heroin on changes
in the extracellular DA and DOPAC concentrations in
the AcbSh between samestrain rats demonstrating
different vulnerability within the addiction and
withdrawal phases of the respective experiment.
METHODS
Animals. Male Sprague–Dawley rats (n = 48, body
mass 250 to 300 g) were obtained from the Animal
Center of the Xiangya Medical College, Central South
University. They were housed in standard breeding
cages (27×21×13.5 cm) maintained at 2025°C,
relative humidity 55%, with an automatic 12h light/
dark cycle. (8 a.m. to 8 p.m.). All rats were allowed to
acclimatize for one week before the experiment.
Behavioral Tests. In the CPP experiments, there
were four identical twochamber Plexiglas boxes
with two equalsize compartments (30×30×30 cm).
One compartment was painted white and had a mesh
floor, while the other compartment was painted black
and had a smooth floor. Two replaceable clapboards
with whiteblack sides were used to separate the
compartments. One replaced clapboard contained a
10 × 10 cm opening that allowed free access to the two
compartments.
The rats were randomly assigned into heroin
treated and control (saline) groups (n = 40 and n =
= 8, respectively). The apparatus was located in a room
separate from the colony room, which was supplied
with white noise (ambient background of 70 dB) in
order to mask extraneous sounds. A video camera and
a remote computer monitor allowed us to measure time
intervals spent by rats in the compartments of the CPP
apparatus.
The preconditioning phase was 3 day long. Every
day, all rats were placed into the CPP apparatus for
30 min with the replaced clapboard. On the 2nd and
3rd days, the time the rats spent in each compartment
was recorded for 15 min, with each entry and exit
being defined as both front paws in the respective
compartment. The average of the two times was
considered the baseline CPP (Pre). Then heroin was
paired with the nonpreferred compartment, and another
side was paired with saline injection. The conditioning
phase was 7 days, and the heroingroup rats were
subjected to a randomly balanced order of conditioning
in which either heroin or saline was first or repeated.
Everyday conditioning training was conducted with
twice heroin and twice equalvolume saline injections,
respectively. Every time the rats were injected with
saline or heroin, they were then placed immediately
for 30 min into the paired compartment. The time
interval between two trains was not shorter than 4 h.
Heroin was administered according to an escalating
dose schedule. Doses within 7 days increased from
0.5 mg/kg on day 1 to 3.5 mg/kg bid i.h. on day 7. Saline
group rats were injected only with an equal volume of
saline and subjected to the same CPP procedure.
On the next after the last conditioning day, each rat
was subjected to a preference test in a drugfree state.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 3 257
DOPAMINE RESPONSIVENESS IN THE NUCL. ACCUMBENS SHELL
The rat was placed within the middle opening of the
replaced clapboard to allow free access of the animal
to the entire apparatus for 15 min. Total times spent in
the white and black compartments were measured. The
difference (sec) between the time spent in the drug
paired compartment within the testing phase and the
preconditioning phase was considered a measure of
the degree of heroininduced conditioning. The drug
influenced preference was taken into account if the
difference was positive.
When the CPP testing phase was terminated,
animals of the studied groups were reclassified into
two groups according to the degree of heroininduced
conditioning. These were the highpreference group
(HP, n = 12) and the low preference group (LP, n =
= 12); each group included 30% of the total number
of animals examined. The HP and LPgroup rats
were injected with heroin (3.5 mg/kg bid i.h) until
microdialysis sample collection was started.
Microdialysis Procedures. Brain microdialysis
experiments were performed as was previously
described. Rats were stereotaxically implanted under
4% pentobarbital sodium (3035 mg/kg) anesthesia
with a CMA/11 guide cannula. This cannula was fixed
in position with three stainless steel screws and dental
acrylic plastic with its tip close to the AcbSh (FP
1.7 mm, ML 0.7 mm; and DV 7.0 mm from the
bregma). A dummy probe was then inserted into the
guide cannula to prevent obstruction.
After recovery from surgery (48 h), the rats were
connected to a microperfusion pump (CMA/110;
CMA/Microdialysis AB, Sweden) and placed into
a cylindrical Plexiglas transparent microdialysis
container (30 cm in diameter; 35 cm in height),
where they were allowed to move freely. The dummy
probe was replaced with a concentric microdialysis
probe (CMA/11, CMA/Microdialysis AB, Sweden;
membrane, 1.0 mm; cutoff, 6000 Dalton; shaft
length, 14 mm). They were inserted through the guide
cannula, extending beyond the cannula tip to maximize
the contact of the dialysis membraneexposed surface
area with the AcbSh.
Ringer solution (140 mM NaCl, 1.2 mM CaCl2,
3.0 mM KCl, and 1.0 mM MgCl2) was perfused
through the syringe pump connected to the probe via a
fluorinated ethylenepropylene tubing (FEP, 0.005″ ID)
at a flow rate of 2.0 μl/min for at least 90 min prior to
the start of sample collections. Samples were collected
30 min and on days 1, 3, 7, and 14 after the last heroin
injection into refrigerated (4°C) microcentrifuge tubes
containing 2.0 µl of hydrochloric acid to prevent
enzymatic breakdown.
Analyses of the dialysate samples were performed
by highperformance liquid chromatography with
a coulometric electrode array system (HPLCEC
CoulArrar5600A; ESA, USA). A standard curve was
plotted according to 100, 50, 20, 10, 1, 0.5, and 0.05
µg/l dopamine standards (Sigma, USA). Correlation
coefficients (r2) for the peak area of concentrations
of the standard curve were calculated using linear
regression. The results showed that the standard linear
curve had satisfactory r2 values (DA: y = 16.157 x,
r2 = 0.9998, and DOPAC: y = 16.619 x, r2 = 0.9992).
An output from the detector was analyzed with a
computer program, and the levels were determined
by comparison with a standard curve. The lower
sensitivity limit for DA was approximately 0.1 µg/l,
and for DOPAC it was 0.2 µg/l.
Histology. After completion of the experimental,
the rats were anesthetized with sodium pentobarbital
and perfused transaortally with 0.9% NaCl for 5 min
followed by 4% paraformaldehyde for 10 min. The
brains were removed, placed in 4% paraformaldehyde
for at least 6 h, and immersed in 30% v/v sucrose
until they sank completely. Coronal 40µmthick
sections were cut with a cryostat, and the placement
of the cannula tip was confirmed by microscopic
examination. Only animals with correctly placed
probes were included in the statistical analyses.
Statistical Analysis. Microdialysis and CPP
numerical data among the experiment (HP and LP)
and control groups were statistically analyzed using
oneway ANOVA followed by posthoc analysis by
means of the Fisher’s protected least significant
difference (PLSD) test. Differences with P < 0.05 were
considered significant.
RESULTS
Changes in the Chronic Heroin- or Saline-
Influenced CPP. The baseline CPP values (Pre) in the
three groups were comparable (P = 0.94). A 7day
long heroin treatment significantly increased the time
spent in the heroinpaired side (MCPP), compared
with that in the control group (P < 0.01, P < 0.05).
The MCPP of the HP group was significantly greater
than that in the LP group (P < 0.01) (Fig. 1).
Effects of Heroin on DA and DOPAC in the
AcbSh. Oneway ANOVA was conducted with respect
to changes in the microdialysis data in different
time points among the HP, LP, and saline control
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 47, № 3258
Ch. WANG, H. CHEN, X. WANG et al.
(SC) groups. Compared with the SC group, the
concentrations of extracellular DA (Fig. 2A ) and
DOPAC (B ) in the AcbSh were significantly higher
at 30 min after the last heroin injection (P < 0.001).
However, the DA concentrations in both HP and LP
groups decreased sharply on days 1 and 3 after the
last injection, while these indices were significantly
lower than in the control group (P < 0.05, P < 0.01).
The DA concentrations in herointreated rats recovered
gradually in a week after the last injection. On days
7 and 14, those were still lower, but there was no
significant difference compared to that in the SC group.
Compared with the LP group, the DA concentration in
the AcbSh of the HP group was significantly higher
after the last injection (P < 0.01), and the two groups
demonstrated no significant differences with respect
to withdrawal (A).
Although the DOPAC level decreased significantly
after withdrawal, this index in the AcbSh of HP rats was
significantly higher than that in LP and SCgroup rats
at all five time points (P < 0.05, P < 0.01). At the same
time, there were no significant differences in the DOPAC
concentration between the LP and SCgroups at many
time points within 14 days of withdrawal (Fig. 2B).
Comparison of the DOPAC/DA Ratios in the
AcbSh. The DOPAC/DA value is believed to be an
important indicator of the DA update rate. Oneway
ANOVA was conducted among the experimental (HP
and LP) groups and SC group with respect to this ratio
at different time points. The DOPAC/DA ratios in the
AcbSh in both HP and LP groups were significantly
higher 30 min after the last heroin injection compared
0
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1.5
1.5
2.0
2.0
2.5
2.5
3.0
3.0
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4.0
5.0
4.5
mg/l
A
*** ***
** **
** **
**
** **
** ** **
*** *
* *
**
Bmg/l
HP HP HPLP
Pre CPP M-CPP
LP
**
**
**
**
*
LPSC SC SC
100
200
300
400
500
600
700
800
sec
F i g. 1. Differences in the conditioned place preference (CPP)
influenced by chronic heroin or saline treatment. Vertical scale)
Actual total times (sec) spent at the nonpreferred side(s). Pre are
values before the treatments, CCP are those after heroin treatment
in the respective group, and MCCP are differences between the
baseline and test CCP values. HP, LP, and SC are the highpreference
group (n = 12), lowpreference group (n = 12), and saline control
group (n = 8), respectively. *P < 0.05,**P < 0.01 in the comparisons
shown. Data in this and subsequent Figures are presented as means
± s.e.m.
Р и с. 1. Розбіжності умовнорефлекторної преференції місця,
зумовлені хронічними введеннями героїну або фізіологічного
розчину.
F i g. 2. Dynamics of changes in the concentrations of extracellular DA (A) and DOPAC (B) in the nucl. accumbens shell (AcbSh) measured
in different experimental groups by in vivo microdialysis at different time points (30 min, days 1, 3, 7, and 14) after the last heroin injection.
In HP, LP, and SC groups, n = 8, n = 7, and n = 6, respectively. ***P < 0.001 (comparison by oneway ANOVA). Other designations are
similar to those in Fig. 1.
Р и с. 2. Динаміка змін зовнішньоклітинних концентрацій дофаміну та дигідроксифенілоцтової кислоти в шкаралупі nucl. accumbens
(AcbSh), оцінюваних у різні моменти часу за допомогою мікродіалізу in vivo.
HP HPLP LPSC SC
30 min 30 minday 1 day 13 37 714 14
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2015.—T. 47, № 3 259
DOPAMINE RESPONSIVENESS IN THE NUCL. ACCUMBENS SHELL
with that in the SC group and then gradually decreased
after withdrawal. However, the LP group demonstrated
no significant difference from the SC group 3 days
after the last injection. At all five monitored time
points, the HP rats had, however, significantly higher
DOPAC/DA ratios than those in LP and SCgroup rats
(P < 0.05, P < 0.01, P < 0.001) (Fig. 3).
DISCUSSION
In this study, all rats of the same strain and kept in
the same environment were treated by chronic heroin
conditioning training. Some rats stayed much longer
at the drug side, while this index for other rats did
not increase considerably (and even decrease).
The dissimilar tendency of the CPP development in
these animals may be considered related to different
vulnerabilities to drug addiction.
Activation of the limbic DA system is an important
mechanism of opioid psychological dependence.
Previous studies also showed that the rewarding effects
of opioids were parallel with the DA concentration
increase in the limbic system. The results showed
that, after chronic heroin treatment in both HP and
LP groups, the concentrations of extracellular DA and
DOPAC in the AcbSh were significantly higher than
those in the control group, indicating that heroin can
induce DA release and its increased metabolism. This is
consistent with previous studies related to opioids [22�.
We also found that the examined DA concentration
significantly decreased after withdrawal, and on
days 1 and 3 of withdrawal it was even significantly
lower than that in the control group. Then this index
gradually recovered after a week, which is consistent
with the majority of observations [23�. This suggests
that the DA concentration gradually decreased after
withdrawal because of the lack of sustained heroin
stimulation. At the same time, the sustained high
concentration state of DA within the addiction phase
led to downregulation of the postsynaptic membrane
DA receptor function by a negative feedback
mechanism. Then, the low functional state of the DA
central system could be the neurobiological basis of
the withdrawal symptoms [1].
The DOPAC concentration and DOPAC/DA ratio are
believed to be effective indicators of activity of the DA
system or DA update rate. We found that, within the
addiction period, the DOPAC/DA ratios in the HP and
LP groups were significantly higher than that in the
control (SC) group, indicating that the DA update rate
in the AcbSh is significantly higher. After withdrawal,
the DOPAC level and DOPAC/DA ratio in rats with
different addiction vulnerabilities demonstrated clear
differentiation. The DOPAC/DA index in the HP group
was significantly higher than that in the control and LP
groups, and so did the DOPAC level, while the latter
after withdrawal and the DOPAC/DA ratio after 3 days
of withdrawal in the LP group showed no significant
difference from the control (SC) group, which
suggested that rats with high addiction vulnerability
had a higher DA reactivity to drugs compared with
lowvulnerability rats. However, a higher DA update
rate also leads to stronger craving for heroin. Results
of other studies on the addiction susceptibility in rats
to alcohol [15], cocaine [14, 18], amphetamine [13],
and morphine [16] also agree with this finding.
The findings in our study indicate that the difference
in susceptibility to heroin addiction in rats depends
on the responsiveness of the DA system to drug
exposure. Heroin HP rats have a higher DA system
responsiveness in the AcbSh, which is possibly one
of the neurobiochemical factors responsible for the
heroin vulnerability and is an individual marker of the
respective differences.
Acknowledgments. This study was supported by the
National Key Basic Research and Development Program
(NKBRDP) of China (2009CB522000), State Key Program
of National Natural Science of China (81130020), National
Nature Science Foundation (30971050) to W. Hao, and
0
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1.6
1.8 *
*
*
*
***
***
** **
**
** **
**
HP LPSC
30 min day 1 3 7 14
F i g. 3. Dynamics of the DOPAC/DA ratios in the AcbSh in diffe rent
experimental groups. Designations are similar to those in Figs. 1
and 2.
Р и с. 3. Міжгрупове порівняння значень відношення дигідро
ксифенілоцтова кислота/дофамін у шкаралупі nucl. аccumbens,
проведене в динаміці.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 47, № 3260
Ch. WANG, H. CHEN, X. WANG et al.
Basic and Frontier Program of the Henan Province of China
(122300410118) to WCS.
The study was carried out in accordance with the statements
of the Council Directive regarding the protection of animals
used for experimental and other scientific purposes (86/609/
EEC, 1986, Strasbourg) and respective regulations of the Ethics
Committee at the Xinxiang Medical University.
The authors of this study, Ch. Wang, H. Chen, X. Wang,
R. Zhang, and W. Hao, confirm that the research and publication
of the results were not associated with any conflicts regarding
commercial or financial relations, relations with organizations
and/or individuals who may have been related to the study, and
interrelations of coauthors of the article.
Ч. Ван1, 2, Х. Чен2, Кс. Ван2, Р. Жан1, В. Хао1, 2
ПІДВИЩЕНА ЧУТЛИВІСТЬ ДО ДОФАМІНУ
В ШКАРАЛУПІ NUCL. ACCUMBENS ЩУРІВ
АСОЦІЙОВАНА З УМОВНОРЕФЛЕКТОРНОЮ
ПРЕФЕРЕНЦІЄЮ МІСЦЯ, СФОРМОВАНОЮ ПІД
ВПЛИВОМ ГЕРОЇНУ
1 Друга лікарня при Медичному університеті Ксінкс’яня,
Ксінкс’янь (Китай).
2 Інститут ментального здоров’я, Друга лікарня Ксіанг’я
при Центральному південному університеті, Чанша
(Китай).
Р е з ю м е
Результати попередніх досліджень продемонстрували,
що змінений під впливом фармакологічних агентів
рівень дофаміну (DA) в шкаралупі nucl. accumbens
(AcbSh) є визначальним фактором для вразливості до
героїнової аддукції у лінійних мишей. Ми досліджували
можливу роль реактивності DAергічної системи AcbSh
у вразливості умовнорефлекторної преференції місця
(УРПМ) щодо героїну у щурів лінї Спрейг–Доулі.
Щури були рандомізовано поділені на «героїнову» та
контрольну групи. Щури першої з них потім додатково
поділи на дві групи відповідно до інтенсивності змін
УРПМ під впливом героїну – тварин з високою та низькою
«героїновою» преференцією (HP та LP). Рівні DA та
дигідроксифенілоцтової кислоти (DOPAC) у позаклітинному
просторі AcbSh оцінювали в динаміці за допомогою
мікродіалізу in vivo. Позаклітинні концентрації DА та
DOPAC у «героїнових» групах через 30 хв після останньої
ін’єкції були істотно вищими, ніж у контролі, але рівень DA
у тварин цих груп швидко знижувався і на першу та третю
добу ставав нижчим порівняно з контролем. Тварини групи
HP порівняно зі щурами групи LP демонстрували вищі
значення індукованого героїном збільшення концентрації
DA через 30 хв після останньої ін’єкції героїну та вищі
рівень DOPAC і відношення DOPAC/DA через 14 діб після
такої ін’єкції. Подібні результати дозволяють вважати, що
різниці в реактивності DAергічної системи в AcbSh можуть
визначати індивідуальні відмінності вразливості щодо
героїнової залежності.
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|
| id | nasplib_isofts_kiev_ua-123456789-148193 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 0028-2561 |
| language | English |
| last_indexed | 2025-12-07T16:28:24Z |
| publishDate | 2015 |
| publisher | Інститут фізіології ім. О.О. Богомольця НАН України |
| record_format | dspace |
| spelling | Wang, Ch. Chen, H. Wang, X. Zhang, R. Hao, W. 2019-02-17T17:05:54Z 2019-02-17T17:05:54Z 2015 Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats / Ch. Wang, H. Chen, X. Wang, R. Zhang, W. Hao // Нейрофизиология. — 2015. — Т. 47, № 3. — С. 255-261. — Бібліогр.: 23 назв. — англ. 0028-2561 https://nasplib.isofts.kiev.ua/handle/123456789/148193 612.826.4:663.991 Previous evidence demonstrated that drug-induced extracellular dopamine (DA) concentrations in the nucl. accumbens shell (AcbSh) might underlie different vulnerabilities to heroin addiction in inbred mice strains. We investigated a potential role of the responsiveness of the DA system in the AcbSh with respect to the vulnerability to heroin-influenced conditioned place preference (CPP) in rats. Animals were randomly assigned to the heroin and saline (control) groups. Heroin-group rats were then re-classified into two groups according to the degree of heroin-induced CPP, high preference (HP) and low-preference (LP) ones. The levels of extracellular DA and dihydroxyphenyl acetic acid (DOPAC) were estimated dynamically by in vivo microdialysis. Compared with the saline group, extracellular DA and DOPAC concentrations in the heroin-treated groups were significantly higher 30 min after the last injection, but the DA level decreased sharply in these groups on days 1 and 3 and became lower than that of the saline group. Compared with LP-group rats, HP-rats displayed a higher heroin-induced increase in the DA concentration 30 min after the last heroin injection and higher DOPAC and DOPAC/DA ratios 14 days after such injection. These results suggest that differences in the DA system responsiveness in the AcbSh may determine individual differences in vulnerability to heroin addiction. Результати попередніх досліджень продемонстрували, що змінений під впливом фармакологічних агентів рівень дофаміну (DA) в шкаралупі nucl. accumbens (AcbSh) є визначальним фактором для вразливості до героїнової аддукції у лінійних мишей. Ми досліджували можливу роль реактивності DA-ергічної системи AcbSh у вразливості умовнорефлекторної преференції місця (УРПМ) щодо героїну у щурів лінї Спрейг–Доулі. Щури були рандомізовано поділені на «героїнову» та контрольну групи. Щури першої з них потім додатково поділи на дві групи відповідно до інтенсивності змін УРПМ під впливом героїну – тварин з високою та низькою «героїновою» преференцією (HP та LP). Рівні DA та дигідроксифенілоцтової кислоти (DOPAC) у позаклітинному просторі AcbSh оцінювали в динаміці за допомогою мікродіалізу in vivo. Позаклітинні концентрації DА та DOPAC у «героїнових» групах через 30 хв після останньої ін’єкції були істотно вищими, ніж у контролі, але рівень DA у тварин цих груп швидко знижувався і на першу та третю добу ставав нижчим порівняно з контролем. Тварини групи HP порівняно зі щурами групи LP демонстрували вищі значення індукованого героїном збільшення концентрації DA через 30 хв після останньої ін’єкції героїну та вищі рівень DOPAC і відношення DOPAC/DA через 14 діб після такої ін’єкції. Подібні результати дозволяють вважати, що різниці в реактивності DA-ергічної системи в AcbSh можуть визначати індивідуальні відмінності вразливості щодо героїнової залежності. This study was supported by the National Key Basic Research and Development Program (NKBRDP) of China (2009CB522000), State Key Program of National Natural Science of China (81130020), National Nature Science Foundation (30971050) to W. Hao, and Basic and Frontier Program of the Henan Province of China (122300410118) to WCS. en Інститут фізіології ім. О.О. Богомольця НАН України Нейрофизиология Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats Підвищена чутливість до дофаміну в шкаралупі nucl. accumbens щурів асоційована з умовнорефлекторною преференцією місця, сформованою під впливом героїну Article published earlier |
| spellingShingle | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats Wang, Ch. Chen, H. Wang, X. Zhang, R. Hao, W. |
| title | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats |
| title_alt | Підвищена чутливість до дофаміну в шкаралупі nucl. accumbens щурів асоційована з умовнорефлекторною преференцією місця, сформованою під впливом героїну |
| title_full | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats |
| title_fullStr | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats |
| title_full_unstemmed | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats |
| title_short | Dopamine Responsiveness in the Nucl. Accumbens Shell and Parameters of the Heroin-Influenced Conditioned Place Preference in Rats |
| title_sort | dopamine responsiveness in the nucl. accumbens shell and parameters of the heroin-influenced conditioned place preference in rats |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/148193 |
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