scholarly journals Metabotropic group II glutamate receptors mediate cue-triggered increases in incentive motivation for reward

2021 ◽  
Author(s):  
Caroline Garceau ◽  
Justine Marsault ◽  
Mike J F Robinson ◽  
Anne-Noël Samaha

AbstractRationaleReward-associated cues can acquire incentive motivational properties and invigorate reward-seeking actions via Pavlovian-to-instrumental transfer (PIT). Glutamatergic neurotransmission mediates the appetitive effects of reward-associated cues. We characterized the expression of PIT and its mediation by metabotropic group II glutamate (mGlu2/3) receptor activity in female and male rats.ObjectivesAcross the sexes, we used PIT procedures to determine i) cue-triggered increases in incentive motivation for water reward (Experiment 1), ii) the respective influences of the mGlu2/3 receptor agonist LY379268 and reward devaluation by satiation on this effect (Experiment 2).MethodsWater-restricted male and female Sprague-Dawley rats learned to lever press for water. Separately, they learned that one of two auditory stimuli predicts free water (CS+ vs CS-). On PIT test days, the CS+ and CS- were presented non-contingently, and we measured effects on lever pressing under extinction (no water). In Experiment 1, we characterized PIT across the sexes. In Experiment 2, we measured PIT after systemic LY379268 administration (0, 0.3 and 1 mg/kg), and water satiation, respectively.ResultsFemale and male rats showed similar PIT, with CS+ but not CS- presentations potentiating water-seeking behaviour. LY379268 (1 mg/kg) attenuated CS+ evoked increases in both water-associated lever pressing and conditioned approach to the water port. Reward devaluation attenuated both water-seeking and CS+ evoked conditioned approach behaviour.ConclusionsThe sexes show similar cue-triggered increases in reward ‘wanting’, and water devaluation suppresses both water seeking and cue-triggered anticipation of water reward. Finally, across the sexes, mGlu2/3 receptor activity mediates cue-triggered increases in reward ‘wanting’.

2021 ◽  
Author(s):  
Caroline Garceau ◽  
Anne-Noël Samaha ◽  
Thomas Cordahi ◽  
Alice Servonnet ◽  
Shaun Yon-Seng Khoo

Rationale: Reward-associated cues can trigger incentive motivation for reward and invigorate reward-seeking behaviour via Pavlovian-to-instrumental transfer (PIT). Glutamate signaling within the basolateral amygdala (BLA) modulates cue-triggered increases in incentive motivation. However, the role of BLA metabotropic group II glutamate (mGlu2/3) receptors is largely unknown. Objectives: In Experiment 1, we characterized cue-triggered increases in incentive motivation for water reward using the PIT paradigm. In Experiment 2, we assessed the influence of intra-BLA microinjections of the mGlu2/3 receptor agonist LY379268 on this effect. Methods: Water-restricted male Sprague-Dawley rats learned to press a lever for water. Separately, they learned to associate one of two auditory cues with free water. On test days, rats could lever press under extinction conditions (no water), with intermittent, non-contingent CS+ and CS- presentations. In Experiment 1, rats were tested under baseline conditions. In Experiment 2, rats received intra-BLA microinjections of LY379268 (0, 3 and 6 μg/hemisphere) before testing. Results: Across experiments, CS+, but not CS- presentations increased water-associated lever pressing during testing, even though responding was reinforced neither by water nor the CS+. Intra-BLA LY379268 abolished both CS+ potentiated pressing on the water-associated lever and CS+ evoked conditioned approach to the site of water delivery. LY379268 did not influence locomotion or instrumental and Pavlovian response rates during intervals between CS presentations or during the CS-, indicating no motor effects. Conclusions: mGlu2/3 receptor activity in the BLA mediates CS-triggered potentiation of incentive motivation for reward, suppressing both CS-induced increases in instrumental pursuit of the reward and anticipatory approach behaviour.


2019 ◽  
Author(s):  
Alice Servonnet ◽  
Giovanni Hernandez ◽  
Cynthia El Hage ◽  
Pierre-Paul Rompré ◽  
Anne-Noël Samaha

ABSTRACTReward-associated stimuli can acquire both predictive and incentive motivational properties. These conditioned stimuli (CS) can then guide reward-seeking behaviour in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) contributes to learning of the predictive value of CS, but less is known about BLA contributions to the incentive motivational properties of appetitive CS. Here we studied the influence of BLA neuron activity on both the predictive and incentive motivational effects of CS. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. We assessed the predictive value to the CS by measuring CS-evoked port entries during Pavlovian conditioning. We assessed CS-evoked incentive motivation by measuring lever-pressing for the CS during instrumental responding sessions. During Pavlovian conditioning, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. This potentiated CS-evoked port entries during conditioning, but suppressed subsequent lever-pressing for the CS. This indicates increased conditioned responding to the CS, but an apparent decrease in incentive motivation for that CS. However, in rats previously naïve to photo-stimulation, pairing BLA-ChR2 stimulations during lever-pressing for the CS intensified responding, indicating enhanced motivation for the CS. Rats did not self-administer BLA-ChR2 stimulations, suggesting that BLA activation does not carry a primary reward signal. Lastly, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. These converging findings suggest that BLA mediated-activity enhances both the predictive and incentive motivational properties of CS, allowing BLA-dependent circuits to guide behaviour in the presence of reward-associated cues.SIGNIFICANCE STATEMENTCues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behaviour, as in over-eating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues are predictive and thus evoke anticipation of future rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both the predictive and motivational effects of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behaviour by both increasing anticipation for impending rewards and making reward cues more attractive.


2020 ◽  
Author(s):  
Joshua L Haight ◽  
Paolo Campus ◽  
Cristina E Maria-Rios ◽  
Allison M Johnson ◽  
Marin S Klumpner ◽  
...  

AbstractRationalePrior research suggests that inputs from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) contribute to the attribution of incentive salience to Pavlovian-conditioned reward cues. However, a causal role for the LHA in this phenomenon has not been demonstrated. In addition, it is unknown which hypothalamic neurotransmitter or peptide system(s) are involved in mediating incentive salience attribution.ObjectivesTo examine: 1) the role of the LHA in the propensity to attribute incentive salience to reward cues, and 2) the role of orexinergic signaling in the PVT on the expression of Pavlovian conditioned approach (PavCA) behavior, a reflection of incentive salience attribution.MethodsMale Sprague-Dawley rats received bilateral excitotoxic lesions of the LHA prior to the acquisition of Pavlovian conditioned approach (PavCA) behavior. A separate cohort of male rats acquired PavCA behavior and were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their conditioned response. The orexin 1 receptor (OX1r) antagonist SB-334867, or the orexin 2 receptor (OX2r) antagonist TCS-OX2-29, were then administered directly into the PVT to assess the effects of these pharmacological agents on the expression of PavCA behavior and on the conditioned reinforcing properties of the Pavlovian reward cue.ResultsLesions of the LHA before training attenuated the development of lever-directed (sign-tracking) behaviors in the PavCA paradigm, without affecting magazine-directed (goal-tracking) behaviors. In STs, administration of the OX1r antagonist into the PVT reduced lever-directed behaviors and increased magazine-directed behaviors; while administration of the OX2r antagonist only reduced lever-directed behaviors. Further, OX2r, but not OX1r, antagonism was able to reduce the incentive motivational value of the conditioned stimulus on a conditioned reinforcement test in STs. The behavior of GTs was unaffected by orexinergic antagonism in the PVT.ConclusionsThe LHA is necessary for the attribution of incentive salience to reward cues and, thereby, the development of a sign-tracking conditioned response. Furthermore, blockade of orexin signaling in the PVT attenuates the incentive value of a Pavlovian reward cue. These data suggest that hypothalamic orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues and promotes maladaptive cue-driven behaviors.


2018 ◽  
Author(s):  
Kurt M. Fraser ◽  
Patricia H. Janak

AbstractThe context in which reward-paired cues are encountered sets the occasion for appropriate reward-seeking but may also spur inappropriate behaviors such as the renewal of drug-seeking. The psychological processes underlying occasion setting remain unclear as contexts are diffuse and difficult to isolate from other stimuli. To overcome this, we modeled a context as a phasic and discrete event – an occasion setter – which allowed for control over its presentation and influence on cue-driven reward-seeking. This allowed us to directly assess how occasion setters, like contexts, regulate the predictive and motivational significance of Pavlovian cues. Male rats (n=50) were trained in a Pavlovian paradigm where the presentation of an ambiguous conditioned stimulus was reinforced only if preceded by an occasion setting cue. We assessed the motivational value of the occasion setter and conditioned stimulus alone or in combination using conditioned reinforcement. Rats showed enhanced conditioned approach to the reward port during the reward-adjacent conditioned stimulus when it was preceded by the occasion setter. When allowed the opportunity, rats responded more to obtain presentations of the conditioned stimulus in combination with the occasion setter than the conditioned stimulus alone. Critically, rats also worked to obtain presentations of the occasion setter alone more than the conditioned stimulus, and this was resistant to manipulations of the value of the occasion setter. We conclude that occasion setting can act via incentive motivational mechanisms and that, apart from resolving predictive information about ambiguous reward-paired cues, occasion setters themselves generate states of appetitive motivation that can facilitate reward-seeking.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.


2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.


2020 ◽  
Vol 19 (2) ◽  
pp. 296-303
Author(s):  
Eni Widayati ◽  
Taufiqurrachman Nasihun ◽  
Azizah Hikma Savitri ◽  
Nurina Tyagita

Objective: The effect of Pimpinela alpina Molk (PaM) on decrease in Bax and Caspase-3 protein expression in liver cells apoptosis have been proven. However, the difference result between 7 and 15 days treatment duration of PaM need to be confirmed. This study aimed to confirm that treatment of PaM during 15 days is more effective decreasing Bax and Caspase-3 protein expression in liver cells following UVB irradiation. Methods: In the post test only control group design, 35 Sprague Dawley male rats, 300 gram body weight were divided into two arms, consisting of three groups respectively. First arm comprise Neg-7, PaM7-100, and PaM7-150. Second arm comprise Neg-15, PaM15-100, and PaM15-150. Nor-G was added as normal control neither exposed to UVB nor PaM treatment. In negative group was only radiated to UVB and PaM groups were exposed to UVB and treatment with 100, and 150 mg PaM per oral for 7 and 15 days respectively. At day 8 (first arm) and 16 (second arm), liver organ was taken and Bax and Caspase-3 protein expression assessed by Immunohistochemical staining method. Result: Post Hoc LSD analysis indicated that Bax and Caspase-3 protein expression in PaM15-100 and PaM15-150 was significant lower compared to that of Nor-G, PaM7-100, and PaM7-150, p < 0.05. Conclusion: Ttreatment of PaM with doses 100 and 150 mg for 15 days was better in decreasing Bax and Caspase-3 protein expression of liver cells following UVB irradiation. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.296-303


2006 ◽  
Vol 83 (3) ◽  
pp. 360-369 ◽  
Author(s):  
Timo Viitamaa ◽  
Antti Haapalinna ◽  
Anders Ågmo

1979 ◽  
Vol 16 (5) ◽  
pp. 574-582 ◽  
Author(s):  
J. J. Berman ◽  
J. M. Rice

A single intraperitoneal dose of methyl(acetoxymethyl)nitrosamine (13 mg/kg body weight) given to 78 5-week-old male rats induced 25 mesotheliomas; two mesotheliomas were found in 67 control rats. All mesotheliomas arose from the peritesticular mesothelium and had a typical microscopic appearance of branching papillary fronds with a collagenous core covered by one or many layers of plump tumor cells. Cytoplasm of tumor cells contained material that reacted positively to a colloidal iron stain and was labile to hyaluronidase. In addition to frank mesotheliomas, 16 lesions, which we called atypical mesothelial proliferations. were found. These consisted of a single focus of plump mesothelial cells overlying an area of thick stroma. Often these foci included short, non-branched papillary projections above the surface of adjacent normal mesothelium. Twelve of the 16 lesions occurred in methyl(acetoxymethyl)nitrosamine-treated rats.


Nanomaterials ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Huy Xuan Ngo ◽  
Quang Ngoc Dong ◽  
Yunpeng Bai ◽  
Jingjing Sha ◽  
Shinji Ishizuka ◽  
...  

Uncalcined/unsintered hydroxyapatite and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) is a new bioresorbable nanomaterial with superior characteristics compared with current bioresorbable materials, including appropriate mechanical properties, outstanding bioactive/osteoconductive features, and remarkably shorter resorption time. Nevertheless, the bone regeneration characteristics of this nanomaterial have not been evaluated in maxillofacial reconstructive surgery. In this study, we used a rat mandible model to assess the bone regeneration ability of u-HA/PLLA/PGA material, compared with uncalcined/unsintered hydroxyapatite and poly-l-lactide acid (u-HA/PLLA) material, which has demonstrated excellent bone regenerative ability. A 4-mm-diameter defect was created at the mandibular angle area in 28 Sprague Dawley male rats. The rats were divided into three groups: u-HA/PLLA/PGA (u-HA/PLLA/PGA graft + defect), u-HA/PLLA (u-HA/PLLA graft + defect), and sham control (defect alone). At 1, 3, 8, and 16 weeks after surgeries, the rats were sacrificed and assessed by micro-computed tomography, histological analysis with hematoxylin and eosin staining, and immunohistochemical analyses. The results confirmed that the accelerated bone bioactive/regenerative osteoconduction of u-HA/PLLA/PGA was comparable with that of u-HA/PLLA in the rat mandible model. Furthermore, this new regenerative nanomaterial was able to more rapidly induce bone formation in the early stage and had great potential for further clinical applications in maxillofacial reconstructive surgery.


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