scholarly journals Role of orexin peptide system in emotional overeating induced by brain reward stimulation in fed rats

2020 ◽  
Vol 6 (1) ◽  
pp. 81-91
Author(s):  
Andrei A. Lebedev ◽  
Yulia N. Bessolova ◽  
Nikolai S. Efimov ◽  
Eugeny R. Bychkov ◽  
Andrei V. Droblenkov ◽  
...  

Introduction: The purpose of this work was to prove that the reaction of food self-deprivation in “fed up” rats is a suitable model for studying the emotional overeating in the experiment. Methods: The self-deprivation reaction, i.e. self-isolation of an animal from food during electrical self-stimulation of the brain, was studied in animals with food deprivation. To reproduce the self-stimulation of the lateral hypothalamus, the male Wistar rats were trained to press a pedal in a Skinner box. After training, the rats received food deprivation, then a feeder was placed in the Skinner box, and a conditioned food reflex was developed in rats within 5 days. Results and discussion: The food self-deprivation reaction was observed in the ”satiated” rats with a current intensity of 10% and above the threshold for self-stimulation. Hungry animals pressed the pedal for hypothalamic self-stimulation and took no notice of the feeding trough. Sulpiride, a dopamine D2 antagonist (5 and 20 mg/kg i.p.), administered to the “satiated” rats decreased both the eating behavior and self-stimulation in food self-deprivation testing. SB-408124, an orexin A receptor antagonist (0.5 mg/ml, 20 μl intranasally) reduced only the number of pellets eaten, but not the number of pedal presses. Conclusion: The orexin A receptors are preferably involved in emotional eating compared with orexin B (OX2R TCS-OX2-29) and D2 dopamine receptors. Because emotional eating is significantly related to clinical eating disorders, like bulimia and binge eating disorder, it seems promising to use drugs of the orexin system to treat and prevent the issue.

2018 ◽  
Vol 16 (2) ◽  
pp. 37-41
Author(s):  
Nikolay S Efimov ◽  
Yulia N Bessolova ◽  
Inessa V Karpova ◽  
Andrei A Lebedev ◽  
Petr D Shabanov

In the protocols of modern pharmacological studies of a self-stimulation reaction in rodents, stimulating electrodes are implanted as a rule unilaterally. The reinforcing properties of the left and right hypothalamus were suggested to be identical. The aim of the study was to clear up if the possibilities of the left and right hypothalamus to produce self-stimulation are similar or not. Methods. The study was carried out on adult male Wistar rats. The electrodes were implanted into the lateral hypothalamus bilaterally. The rats, in which an approach reaction was observed, learned self-stimulation in the Skinner box with stimulation of the left or right hypothalamus as a reinforcing agent descending thresholds of stimulation up to minimal one. Results. Self-stimulation of the left hypothalamus gave an approach reaction in the majority of rats (81.8%), self-stimulation reaction was developed in 72.7% of rats. Only 46.2% rats reacted on stimulation of the right hypothalamus, self-stimulation reaction was developed in 30.8% of rats. The thresholds of positive and negative reactions registered after electrical stimulation of both sides of hypothalamus were significantly differed (H(3, N = 31) = 14,92; p = 0,002). And these changes were not connected with lateralization but with sign of reaction: in general the thresholds of approach reaction were higher than thresholds of avoidance. Conclusion. In the paper, the fact of different possibility of approach reaction and self-stimulation development as a result of electrical stimulation of the left and right hypothalamus in rats has been described. After stimulation of the left hypothalamus, a possibility to receive positive reaction and to form self-stimulation on its basis is higher than after stimulation of the right hypothalamus. (For citation: Efimov NS, Bessolova YN, Karpova IV, et al. Asymmetry of reinforcing properties of the lateral hypothalamus in the self-stimulation test. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):37-41. doi: 10.17816/RCF16237-41).


2018 ◽  
Author(s):  
Julie Corre ◽  
Ruud van Zessen ◽  
Michaël Loureiro ◽  
Tommaso Patriarchi ◽  
Lin Tian ◽  
...  

AbstractThe dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we use genetically encoded DA and calcium indicators as well as cFos to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.


1971 ◽  
Vol 29 (2) ◽  
pp. 655-665 ◽  
Author(s):  
Irmingard I. Lenzer

The effects of two concurrently changing drive variables, food deprivation and estrogen level, on the self-stimulation rate in the hypothalamus, septum, caudate nucleus, or dorsal hippocampus of 15 female albino rats were studied. When the effects of hunger were calculated using only scores on days of diestrus and the effects of estrogen were calculated using only scores on days of 0-hr. food deprivation, the correlation of these hunger and estrogen effects amounted to 0.67. When the hunger effects were calculated using only scores on days of estrus and these hunger effects correlated with the previously calculated estrogen effects, the correlation amounted to −0.49. These results are consistent with the concept of diffuse overlapping motivational systems in the brain. Controls indicated that the changes in self-stimulation rate were not artifacts of changes in nonspecific activity.


2017 ◽  
Vol 19 (1) ◽  
pp. 37-45
Author(s):  
Petr D Shabanov ◽  
Andrei Andreevich Lebedev ◽  
Vitalii Ivanovich Morozov ◽  
Sergei Vladimirivich Azarenko

Male Wistar rats were implanted bipolar electrodes into the lateral hypothalamus to study self-stimulation reaction in the Skinner box and microcannulas into the right lateral ventricle and structutes of the paraamygdalar complex (bed nucleus of stria terminalis, central nucleus of amygdala or nucleus accumbens) to study central effects of orexin (5 µg in 5 µl i. v. for an injection) on the reinforcing properties of pharmacological drugs. Intraperitoneal administration of trimeperidine (3 mg/kg), a synthetic opioid, was shown to increase self-stimulation of the lateral hypothalamus in the Skinner box (number of pedal pressings for 10 min) by 51.8%, and sulpiride (5 mg/kg, a small dose), an antagonist of D2 dopamine receptors, did not change but in the large dose (20 mg/kg) decreased self-stimulation by 49.3% (a number of pedal pressings, or self-stimulation frequency within 10 min). At the same time, SB-408124, an antagonist of OX1R receptors and its combination with orexin did not change self-stimulation indexes after intrastructural administration into the bed nucleus of stria terminalis, central nucleus of amygdala or nucleus accumbens. On the background of blockade of OX1R receptors by SB-408124 (1 µg for all structures) trimeperidine reduced their activating action on self-stimulation reaction. Sulpiride (5 mg/kg i. p., a dose not affecting self-stimulation reaction) blocked activating action of trimeperidine after blockade OX1R receptors by SB-408124 (1 µg). The data obtained can suggest that OX1R receptors participate in the reinforcing effects of synthetic opioid trimeperidine and the blockade of them by SB-408124 potentiate antagonist effects of sulpiride on self-stimulation (4 tables, bibliography: 23 refs).


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Julie Corre ◽  
Ruud van Zessen ◽  
Michaël Loureiro ◽  
Tommaso Patriarchi ◽  
Lin Tian ◽  
...  

The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.


2020 ◽  
Vol 17 (4) ◽  
pp. 57-64
Author(s):  
Petr D. Shabanov ◽  
Sergei V. Azarenko ◽  
Vitalii I. Morozov ◽  
Yulia N. Bessolova ◽  
Andrei A. Lebedev

Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B18-28 in rats. Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 g, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula. Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 g, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 g i.v.). Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.


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