scholarly journals Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

2018 ◽  
Author(s):  
Julie Corre ◽  
Ruud van Zessen ◽  
Michaël Loureiro ◽  
Tommaso Patriarchi ◽  
Lin Tian ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Causal Link ◽  
The Self ◽  
Dopamine Neurons ◽  
Self Administration ◽  
Gaba Neurons ◽  
Calcium Indicators ◽  
Compulsive Consumption ◽  
Self Stimulation ◽  
Stimulation Of

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.

scholarly journals Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Julie Corre ◽  
Ruud van Zessen ◽  
Michaël Loureiro ◽  
Tommaso Patriarchi ◽  
Lin Tian ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Causal Link ◽  
The Self ◽  
Dopamine Neurons ◽  
Self Administration ◽  
Gaba Neurons ◽  
Calcium Indicators ◽  
Compulsive Consumption ◽  
Self Stimulation ◽  
Stimulation Of

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.

Features of the involvement of the dopamine and serotonin brain systems in positive and negative emotional states in rats

2020 ◽  
Vol 18 (2) ◽  
pp. 123-130
Author(s):  
Eugenii R. Bychkov ◽  
Andrei A. Lebedev ◽  
Nikolai S. Efimov ◽  
Artyem S. Kryukov ◽  
Inessa V. Karpova ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Lateral Hypothalamus ◽  
Treatment Strategies ◽  
Emotional Reactions ◽  
Aversive Stimulation ◽  
Male Rats ◽  
Emotional States ◽  
Neuropsychiatric Diseases ◽  
Self Stimulation ◽  
Stimulation Of

The aim was to study the effect of rewarding and aversive stimulation of lateral hypothalamus on the turnover of monoamines in the terminal structures of the mesocorticolimbic and nigrostriatal systems: the nucleus accumbens (NAc) and striatum (St). The Wistar male rats were implanted electrodes in the lateral hypothalamus and further trained in self-stimulation test. Animals were also selected on aversive emotional reactions were observed after pressing the pedal for self-stimulation. Subsequently, forced stimulation was performed for 5 minutes and the animals were decapitated. The content of norepinephrine, dopamine (DA) and its metabolites 3,4-dioxiphenylacetic acid (DOPАС) and homovanilinic acid, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens and striatum were determined by high performance liquid chromatography with electrochemical detection. Positive and aversive stimulation of lateral hypothalamus decreased the level of DA in the NAc, however, only stimulation of the positive emotiogenic zone increased the DA and 5-HT turnover in the NAc, as evidenced by an increase in the DOPАС/DA and 5-HIAA/SER ratios, respectively. Rewarding and aversive stimulation decreased the level of 5-HT in St, however, only rewarding stimulation decreased the St level of 5-HIAA compared to control and animals with aversive stimulation. Rewarding stimulation increased the turnover of serotonin in St, as evidenced by the increase of 5-HIAA/5-HT ratios. The activity of the noradrenergic system did not change after rewarding and aversive stimulation. Thus, both rewarding and aversive electrical stimulation increases the turnover of DA and 5-HT in NAc and St. However, these changes are more significant after rewarding stimulation. DA turnover increases more in NAc, and 5-HT turnover in St. The data obtained indicate the specificity of the dopaminergic and serotonergic involvement for the formation of a modality of emotional reactions. Data may provide guidance for developing treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.

scholarly journals Differential expression of long-term potentiation among identified inhibitory inputs to dopamine neurons

2017 ◽  
Vol 118 (4) ◽  
pp. 1998-2008 ◽  
Author(s):  
DeNard V. Simmons ◽  
Alyssa K. Petko ◽  
Carlos A. Paladini
Keyword(s):  
Nucleus Accumbens ◽  
Adenylyl Cyclase ◽  
Ventral Tegmental Area ◽  
Cyclic Gmp ◽  
Long Term Potentiation ◽  
Dopamine Neurons ◽  
Gaba Neurons ◽  
Tegmental Nucleus ◽  
Term Potentiation

The in vivo firing pattern of ventral tegmental area (VTA) dopamine neurons is controlled by GABA afferents originating primarily from the nucleus accumbens (NAc), rostromedial tegmental nucleus (RMTg), and local GABA neurons within the VTA. Although different forms of plasticity have been observed from GABA inputs to VTA dopamine neurons, one dependent on cyclic GMP synthesis and the other on adenylyl cyclase activation, it is unknown whether plasticity is differentially expressed in each. Using an optogenetic strategy, we show that identified inhibitory postsynaptic currents (IPSCs) from local VTA GABA neurons and NAc afferents exhibit a cyclic GMP-dependent long-term potentiation (LTP) that is capable of inhibiting the firing activity of dopamine neurons. However, this form of LTP was not induced from RMTg afferents. Only an adenylyl cyclase-mediated increase in IPSCs was exhibited by all three inputs. Thus discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons. NEW & NOTEWORTHY We describe a mapping of plasticity expression, mediated by different mechanisms, among three distinct GABA afferents to ventral tegmental area (VTA) dopamine neurons: the rostromedial tegmental nucleus, the nucleus accumbens, and the local GABA neurons within the VTA known to synapse on VTA dopamine neurons. This work is the first demonstration that discrete plasticity mechanisms recruit overlapping but different subsets of GABA inputs to VTA dopamine neurons.

scholarly journals Asymmetry of reinforcing properties of the lateral hypothalamus in the self-stimulation test

2018 ◽  
Vol 16 (2) ◽  
pp. 37-41
Author(s):  
Nikolay S Efimov ◽  
Yulia N Bessolova ◽  
Inessa V Karpova ◽  
Andrei A Lebedev ◽  
Petr D Shabanov
Keyword(s):  
Electrical Stimulation ◽  
Lateral Hypothalamus ◽  
The Self ◽  
Stimulation Test ◽  
Reinforcing Agent ◽  
Male Wistar Rats ◽  
Left And Right ◽  
The Right ◽  
Self Stimulation ◽  
Stimulation Of

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).

scholarly journals INTERACTION BETWEEN OREXIN AND OPIOIDS SYSTEMS OF THE STRUCTURES OF PARAAMYGDALAR COMPLEX IN THE REINFORCING EFFECTS OF SPONTANEOUS AND ACTIVATED SELF-STIMULATION OF THE LATERAL HYPOTHALAMUS

2017 ◽  
Vol 19 (1) ◽  
pp. 37-45
Author(s):  
Petr D Shabanov ◽  
Andrei Andreevich Lebedev ◽  
Vitalii Ivanovich Morozov ◽  
Sergei Vladimirivich Azarenko
Keyword(s):  
Nucleus Accumbens ◽  
Lateral Hypothalamus ◽  
Intraperitoneal Administration ◽  
Central Nucleus ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Reinforcing Effects ◽  
Skinner Box ◽  
Self Stimulation ◽  
Stimulation Of

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).

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