scholarly journals Resting-state dopaminergic cell firing in the ventral tegmental area negatively regulates affiliative social interactions in a developmental animal model of schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hidekazu Sotoyama ◽  
Hisaaki Namba ◽  
Yutaro Kobayashi ◽  
Taku Hasegawa ◽  
Dai Watanabe ◽  
...  
Keyword(s):  
Social Interaction ◽  
Ventral Tegmental Area ◽  
Resting State ◽  
Dopaminergic Neurons ◽  
Dopamine Release ◽  
Negative Symptoms ◽  
Unit Recording ◽  
Dopaminergic Cell ◽  
Cell Firing ◽  
Ventral Tegmental

AbstractHyperdopaminergic activities are often linked to positive symptoms of schizophrenia, but their neuropathological implications on negative symptoms are rather controversial among reports. Here, we explored the regulatory role of the resting state-neural activity of dopaminergic neurons in the ventral tegmental area (VTA) on social interaction using a developmental rat model for schizophrenia. We prepared the model by administering an ammonitic cytokine, epidermal growth factor (EGF), to rat pups, which later exhibit the deficits of social interaction as monitored with same-gender affiliative sniffing. In vivo single-unit recording and microdialysis revealed that the baseline firing frequency of and dopamine release from VTA dopaminergic neurons were chronically increased in EGF model rats, and their social interaction was concomitantly reduced. Subchronic treatment with risperidone ameliorated both the social interaction deficits and higher frequency of dopaminergic cell firing in this model. Sustained suppression of hyperdopaminergic cell firing in EGF model rats by DREADD chemogenetic intervention restored the event-triggered dopamine release and their social behaviors. These observations suggest that the higher resting-state activity of VTA dopaminergic neurons is responsible for the reduced social interaction of this schizophrenia model.

Functional connectivity of the ventral tegmental area and avolition in schizophrenia: A resting state functional MRI study

2017 ◽  
Vol 41 (S1) ◽  
pp. S196-S196
Author(s):  
G.M. Giordano ◽  
M. Stanziano ◽  
A. Mucci ◽  
M. Papa ◽  
S. Galderisi
Keyword(s):  
Functional Connectivity ◽  
Ventral Tegmental Area ◽  
Functional Mri ◽  
Resting State ◽  
Negative Symptoms ◽  
Real Life ◽  
Fundamental Aspect ◽  
Deficit Syndrome ◽  
Quality Of Life Scale ◽  
Ventral Tegmental

IntroductionImpaired motivation is considered a fundamental aspect of the Avolition domain of negative symptoms. The ventral tegmental area (VTA) contains the highest number of DA neurons projecting to the brain areas involved in motivation-related processes.AimThe aim of our study was to investigate by functional MRI the resting-state functional connectivity (RS-FC) of the VTA in patients with schizophrenia and its relationships with real-life motivation and avolition.MethodThe RS-FC was investigated in 22 healthy controls (HC) and in 26 schizophrenia patients (SCZ) treated with second generation antipsychotics only and divided in high (HA = 13) and low avolition (LA = 13) subgroups. We used the Quality of Life Scale and the Schedule for the Deficit Syndrome to assess real-life motivation and avolition, respectively.ResultsHA, as compared to LA and HC, showed a reduced RS-FC of VTA with the right ventrolateral prefrontal cortex (R VLPFC), right posterior insula (R pINS) and right lateral occipital cortex (R LOC). The RS-FC for these regions was positively correlated with motivation in the whole sample and negatively correlated with avolition in schizophrenia patients.ConclusionOur findings demonstrate that motivational deficits in schizophrenia patients are linked to reduced functional connectivity in the DA circuit involved in retrieval of the outcome values of different actions to guide behavior. Further characterization of the factors modulating the functional connectivity in this circuit might foster the development of innovative treatments for avolition.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Pedro Espinosa ◽  
Roxana A. Silva ◽  
Nicole K. Sanguinetti ◽  
Francisca C. Venegas ◽  
Raul Riquelme ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Tyrosine Hydroxylase ◽  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Dopamine Release ◽  
Male Rats ◽  
Midbrain Dopaminergic Neurons ◽  
Dopamine Content ◽  
Ventral Tegmental

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

scholarly journals Smoke Extracts and Nicotine, but not Tobacco Extracts, Potentiate Firing and Burst Activity of Ventral Tegmental Area Dopaminergic Neurons in Mice

2011 ◽  
Vol 36 (11) ◽  
pp. 2244-2257 ◽  
Author(s):  
Fabio Marti ◽  
Ouafa Arib ◽  
Carole Morel ◽  
Virginie Dufresne ◽  
Uwe Maskos ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Burst Activity ◽  
Ventral Tegmental

Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area

Life Sciences ◽  
2005 ◽  
Vol 77 (6) ◽  
pp. 635-649 ◽  
Author(s):  
B. Prieto-Gómez ◽  
A.M. Vázquez-Alvarez ◽  
J.L. Martínez-Peña ◽  
C. Reyes-Vázquez ◽  
P.B. Yang ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopaminergic Neurons ◽  
Glutamatergic Transmission ◽  
Ventral Tegmental

Cardiovascular depressor responses to stimulation of substantia nigra and ventral tegmental area

1997 ◽  
Vol 273 (6) ◽  
pp. H2549-H2557 ◽  
Author(s):  
Gilbert J. Kirouac ◽  
John Ciriello
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Intravenous Administration ◽  
Dopaminergic Neurons ◽  
Cardiovascular Responses ◽  
Receptor Blocker ◽  
Transitional Region ◽  
Pars Lateralis ◽  
Ventral Tegmental ◽  
Stimulation Of

Experiments were done in α-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect ofl-glutamate (Glu) stimulation of the substantia nigra (SN) and ventral tegmental area (VTA) on arterial pressure (AP) and heart rate (HR). Glu stimulation of the SN pars compacta (SNC) elicited decreases in both mean AP (MAP; −18.9 ± 1.3 mmHg; n = 52) and HR (−26.1 ± 1.6 beats/min; n = 46) at 81% of the sites stimulated. On the other hand, stimulation of the SN pars lateralis or pars reticulata did not elicit cardiovascular responses. Stimulation of the adjacent VTA region elicited similar decreases in MAP (−18.0 ± 2.6 mmHg; n = 20) and HR (−25.4 ± 3.8 beats/min; n = 17) at ∼74% of the sites stimulated. Intravenous administration of the dopamine D2-receptor antagonist raclopride significantly attenuated both the MAP (70%) and the HR (54%) responses elicited by stimulation of the transitional region where the SNC merges with the lateral VTA (SNC-VTA region). Intravenous administration of the muscarinic receptor blocker atropine methyl bromide had no effect on the magnitude of the MAP and HR responses to stimulation of the SNC-VTA region, whereas administration of the nicotinic receptor blocker hexamethonium bromide significantly attenuated both the depressor and the bradycardic responses. These data suggest that dopaminergic neurons in the SNC-VTA region activate a central pathway that exerts cardiovascular depressor effects that are mediated by the inhibition of sympathetic vasoconstrictor fibers to the vasculature and cardioacceleratory fibers to the heart.

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