Behavioural Brain Research 269 (2014) 20–27

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Behavioural Brain Research

jou rnal homepage: www.elsevier.com/locate/bbr

Research report

Delta- receptor blockade in the ventral pallidum increases

perceived palatability and consumption of saccharin solution in rats

∗

Tadashi Inui , Tsuyoshi Shimura

Division of Behavioral Physiology, Department of Behavioral Sciences, Graduate School of Human Sciences, Osaka University, 1-2 Yamadaoka, Suita, Osaka

565-0871, Japan

h i g h l i g h t s

•

We examined the role of delta-opioid receptors in the VP in ingestive behaviour.

•

We used the delta- antagonist naltrindole.

•

Naltrindole injection increased the consumption of a saccharin solution.

•

Naltrindole injection elevated perceived palatability for the saccharin solution.

•

Naltrindole injection caused no changes in aversion to saccharin CS in CTA.

a r t i c l e i n f o a b s t r a c t

Article history: The ventral pallidum (VP) is involved in ingestive behaviour. It receives dense GABAergic projections from

Received 17 December 2013

the nucleus accumbens. GABAergic terminals in the VP co-express , an endogenous ligand

Received in revised form 3 April 2014

of delta-opioid receptors. The role of the delta-opioid receptors in the VP in the context of ingestive

Accepted 5 April 2014

behaviour remains unclear, in contrast to the well-understood involvement of the mu-opioid receptors.

Available online 13 April 2014

We used the single-bottle test to examine the effects of VP microinjections of the delta-opioid recep-

tor antagonist naltrindole on consumption of a saccharin solution. Naltrindole injections significantly

Keywords:

increased the intake of saccharin, but not water, during a 2-h test session. We also investigated perceived

Ventral pallidum

palatability of saccharin using a taste reactivity test. The drug treatments increased ingestive responses

Delta-opioid receptor

Naltrindole to intraorally infused saccharin. Further experimentation explored the role of VP delta-opioid receptors

Taste palatability in behavioural responses to saccharin that were previously paired with malaise upon the retrieval of con-

Consumption behavior ditioned taste aversion (CTA). Naltrindole-injected rats exhibited longer latency for the first occurrence

Conditioned taste aversion of aversive responses than vehicle-injected control rats. However, there was no between-group differ-

ence in total aversive responses. These results suggest that naltrindole injections into the VP induce an

enhancement of perceived palatability of a normally preferred saccharin solution, and thereby facilitate

consumption of the solution. On the other hand, delayed aversive responses to the conditioned aver-

sive saccharin suggest that the delta-opioid receptors in the VP mediate the initiation of aversive taste

reactivity responses to the conditioned stimulus upon CTA retrieval.

© 2014 Elsevier B.V. All rights reserved.

1. Introduction that blockade of GABAergic transmission in the VP elevates the

intake of normally palatable saccharin solution [7] and conditioned

The ventral pallidum (VP), a component of the ventral striatopal- aversive saccharin solution [8]. In addition, it has been demon-

lidal system, receives dense neural projections from the nucleus strated that the stimulation of mu-opioid receptors in the VP

accumbens (NAc) [1–3]. The predominant cell in the NAc is the increases the consumption of sucrose and saccharin solutions and

GABAergic medium spiny neuron (MSN), which comprises 95% of the subjective palatability of them [7,9,10]. The administration of

the NAc cell population [4–6]. Recently, our studies have shown a mu-opioid receptor agonist into the VP abolishes the influence

of GABA-induced inhibition of VP neurons [11,12]. These findings

suggest that the interaction of GABA released from the nerve termi-

∗ nals of NAc-projective neurons with mu-opioid receptors in the VP

Corresponding author. Tel.: +81 6 6879 8049; fax: +81 6 6879 8049.

is involved in the ingestive behaviour of sweet-tasting solutions.

E-mail addresses: [email protected], [email protected] (T. Inui).

http://dx.doi.org/10.1016/j.bbr.2014.04.005

0166-4328/© 2014 Elsevier B.V. All rights reserved.

T. Inui, T. Shimura / Behavioural Brain Research 269 (2014) 20–27 21

Previous anatomical studies have reported that the NAc is using standard stereotaxic techniques and were secured to the

among the regions that exhibit the highest concentrations of pre- skull with stainless steel screws and dental cement. The coordi-

(PPE) mRNA expression in the brain [13,14]. In the nates were selected according to the stereotaxic atlas of Paxinos

VP, enkephalin is co-localized with GABA [15–17]. The and Watson [33]. Guide cannulae were aimed at the ventral

are the endogenous opioid ligands that exhibit the highest affin- pallidum (anteroposterior, −0.3 mm from the bregma; mediolat-

ity for delta receptors [18–21]. An immunohistochemical study eral, ±2.4 mm; dorsoventral, −7.2 mm from the bregma) with the

has demonstrated the presence of mu but not delta receptors on skull level. After surgery, dummy cannulae (C315DC; PlasticsOne,

enkephalinergic terminals in the VP, while both mu and delta opioid Roanoke, VA, USA) were placed in the guide cannulae to pre-

receptors were identified on postsynaptic structures in this region vent occlusion. Rats participating in the TR and CTA tests were

[22]. Although several lines of evidence indicate that mu-opioid implanted with a size-10 unilateral intraoral (IO) tube (Igarashi

receptors in the VP play an important role in ingestive behaviour, Medical Industry, Tokyo, Japan) for fluid infusions just before the

the role of the delta-opioid receptors remains unknown. implantation of guide cannulae. The IO tube was inserted into the

The activation of opioid receptors in the brain is gener- temporalis muscle and opened into the oral cavity just lateral to

ally thought to inhibit neurons by causing G-protein-regulated the first molar. Each rat received subcutaneous injections of sterile

inward-rectifying potassium channels [23–28]. An in vitro elec- penicillin (0.4 ml, 5000 U; Meiji Seika Pharma, Tokyo, Japan) imme-

trophysiological study demonstrated that the application of the diately after surgery. Rats were allowed 1 week of recovery before

delta-opioid receptor agonist, [D-Pen2,5]-enkephalin (DPDPE) sup- behavioural testing. When microinjection was prevented owing to

presses the activities of the VP neurons [29], suggesting that clogging of the guide cannulae before behavioural testing of an

enkephalin has inhibitory effects on postsynaptic cells as well as animal was completed, we excluded the data from that rat.

GABA in the VP. Because microinjection of the GABAA receptor

antagonist bicuculline into the VP induced increased saccharin

2.3. Behavioural procedures

intake in our previous study [7], we assumed that blockade of delta-

opioid receptors in the VP would facilitate the consumption of a

2.3.1. Single-bottle test

sweet-tasting solution.

Animals were deprived of water for 17 h (n = 10) and trained

This study aimed to examine the effects of microinjection of

to drink distilled water from a bottle during a 2-h session. The

a delta-opioid , naltrindole, into the VP on

bottle consisted of a 50-ml plastic syringe (Terumo) and a stain-

the intake behaviour of saccharin solution and water using a

less steel spout (TV-25, CLEA, Tokyo, Japan). Two hours after the

single-bottle test. We also investigated the effects of naltrindole

training, the rats were given supplementary water for 4 h. These

injections on perceived palatability of the saccharin solution using

training sessions were performed on five consecutive days. On Day

the taste reactivity (TR) test, which is a standard technique for the

6, the rats (n = 6) were presented with a 5-mM saccharin solu-

behavioural estimation of taste palatability [30]. Furthermore, we

tion instead of water for the attenuation of taste neophobia. They

also clarified whether the application of naltrindole to the VP affects

received microinjections of naltrindole dissolved in saline (0, 10,

aversion to saccharin solution as a conditioned stimulus (CS) in the

or 100 ng naltrindole/0.25 ␮l saline/side) into the VP on Days 7, 10,

conditioned taste aversion (CTA) paradigm, because a series of our

and 13. Another group of rats (n = 10) was presented with water on

recent studies revealed that GABAergic projections from the NAc

Day 5 and the test days.

to the VP mediate aversion to the CS saccharin upon the retrieval

On the test days, the dummy cannulae were removed and injec-

of CTA [8,31,32].

tor cannulae were inserted into the guide cannulae. The injector

cannulae, which extruded 1 mm from the tip of the guide cannulae,

␮

2. Materials and methods were connected to 10- l gastight microsyringes (1701N; Hamilton,

Reno, NV, USA) on a microsyringe pump (KDS210; KD Scientific,

2.1. Animals Holliston, MA, USA) by a polyethylene tube (PE10; Becton, Dickin-

son and Company, Sparks, MD, USA) and Byton connector (JB-30;

®

The subjects were 44 male Wistar rats, weighing between 250 Eicom, Kyoto, Japan) filled with Fluorinert (FC-40; Sumitomo 3 M,

␮

and 275 g at the beginning of experiments. Upon arrival, rats were Tokyo, Japan). The drug was injected at a rate of 0.25 l/min for

housed individually in clear plastic cages. Subjects were main- 1 min. To prevent backflow of the injected drug solution, the injec-

tained on a 12:12-h light/dark cycle (lights on from 07:00 to 19:00) tor cannulae were left in place for 1 min. The dummy cannulae were

with food and water available ad libitum except where noted. backed into the guide cannulae immediately after the injector can-

Behavioural testing was performed between 10:00 and 17:00, dur- nulae were removed. Immediately after microinjection of the drug,

ing the light cycle. All animals were handled in accordance with the rats were presented with a saccharin solution for 2 h. We mea-

the procedures outlined in the Guide for the Care and Use of Lab- sured the consumption of this solution every 30 min. Each animal

oratory Animals (National Institute of Health Guide). Approval for received all naltrindole dosages in random order.

this study was obtained from the institutional committee on animal

research (the Animal Research Committee at Osaka University).

2.3.2. Taste reactivity (TR) test

The (TR) test is a standard technique used to estimate perceived

2.2. Surgery palatability of solutions of different taste types, and was devel-

oped by Grill and Norgren [30]. Rodents exhibit typical orofacial

For implantation of guide cannulae for drug injections, ani- and somatic responses to pleasant- and unpleasant-tasting solu-

mals were anaesthetized with 50 mg/kg pentobarbital sodium tions. These responses are divided into two categories: ingestive

®

(Somnopentyl ; Kyoritsu Seiyaku, Tokyo, Japan) and intramus- and aversive. Ingestive responses are elicited by sweet, mild, salty,

cularly injected with hydrochloride (Daiichi Sankyo and other pleasant-tasting solutions. They include the following

Propharma, Tokyo, Japan). The anaesthetized rats were mounted three typical responses: tongue protrusion, lateral tongue protru-

in a stereotaxic frame (SR-8; Narishige Scientific Instrument Lab- sions, and paw licking. In contrast, aversive responses are induced

oratory, Tokyo, Japan) using blunt ear bars, with the skull levelled by bitter, strong, sour and other unpleasant-tasting solutions. They

between bregma and lambda. Bilateral stainless steel guide can- include the following six responses: gaping, chin rubbing, head

nulae (C315G; PlasticsOne, Roanoke, VA, USA) were implanted shaking, and forelimb flailing. Download English Version: https://daneshyari.com/en/article/6258020

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