Endogenous enkephalin modulation of dopamine neurons in ventral tegmental area

1986 ◽  
Vol 251 (2) ◽  
pp. R243-R249 ◽  
Author(s):  
P. W. Kalivas ◽  
R. Richardson-Carlson
Keyword(s):  
Nucleus Accumbens ◽  
Motor Activity ◽  
Ventral Tegmental Area ◽  
Physiological Role ◽  
Dopamine Metabolism ◽  
Dopamine Neurons ◽  
Spontaneous Motor Activity ◽  
Opioid Antagonist ◽  
Dopamine Antagonist ◽  
Ventral Tegmental

Many lines of evidence support the possibility that the opioid pentapeptides Met- and Leu-enkephalin can modulate dopamine neurons in the ventral tegmental area (VTA). Thus microinjection of enkephalin analogues into the VTA of rats produces a dopamine-dependent increase in spontaneous motor activity and an increase in dopamine metabolism in certain mesolimbic dopamine terminal fields, such as the nucleus accumbens. To determine if these effects can be produced by endogenous enkephalins, an enkephalinase A inhibitor, thiorphan, was microinjected into the VTA to inhibit enkephalin metabolism. Thiorphan produced a dose-dependent (0.3-3.33 micrograms) increase in spontaneous motor activity that was blocked by pretreatment with the opioid antagonist naloxone (2.0 mg/kg ip) or the dopamine antagonist haloperidol (0.1 mg/kg ip). Thiorphan injection into the VTA increased dopamine metabolism in the nucleus accumbens, prefrontal cortex, and septum but not in the striatum. In all brain regions the increase in dopamine metabolism was blocked by pretreatment with naloxone. These data demonstrate that endogenous enkephalin in the VTA can increase the activity of A10 dopamine neurons, supporting a physiological role for enkephalin in mesolimbic and mesocortical dopamine-mediated behaviors.

scholarly journals Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

2022 ◽  
Author(s):  
Imre Kalló ◽  
Azar Omrani ◽  
Frank J. Meye ◽  
Han de Jong ◽  
Zsolt Liposits ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Medial Prefrontal Cortex ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Dopamine Neurons ◽  
Regulatory Processes ◽  
Ventral Tegmental ◽  
Shell Part

AbstractOrexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

Treatment and management of patients with schizophrenia

2020 ◽  
pp. 668-678
Author(s):  
Joseph P. McEvoy ◽  
Kammarauche Asuzu ◽  
Daniel W. Bradford ◽  
Oliver Freudenreich ◽  
Katherine Moyer
Keyword(s):  
Ventral Tegmental Area ◽  
Brain Damage ◽  
Standard Care ◽  
Sensory Experience ◽  
Dopamine Neurons ◽  
Dopamine Antagonist ◽  
Low Grade ◽  
Sustained Remission ◽  
Motor Functioning ◽  
Ventral Tegmental

In schizophrenia, the years before psychosis are morbid, not premorbid. Widespread, low-grade corruption of circuitry (brain damage) occurs, resulting in enduring deficits in cognitive, social, and motor functioning and motivation. These deficits persist during patients’ lifetime and do not respond to medication or talking. Expectations of patients’ functioning must be modified (reduced); interactions and environments must be accommodated to support best residual functioning, and prostheses (mechanical or actions of others) must replace functions no longer available. One of the deficits—anosognosia—interferes with treatment efforts. When the circuits managing dopamine neurons in the ventral tegmental area are corrupted, storms of dopamine imbue random items of sensory experience and intrapsychic life with salience—psychosis appears. Early and uninterrupted dopamine antagonist medication results in sustained remission of psychosis but is rarely achieved because of the inadequacies of standard care. Enduring engagement by multi-disciplinary teams is the necessary response to the neurobiology of schizophrenia.

Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice

2020 ◽  
Vol 133 (2) ◽  
pp. 377-392
Author(s):  
Gaolin Qiu ◽  
Ying Wu ◽  
Zeyong Yang ◽  
Long Li ◽  
Xiaona Zhu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Medial Prefrontal Cortex ◽  
Repeated Measures ◽  
Intraperitoneal Injection ◽  
Dopamine Neurons ◽  
Patch Clamp Recording ◽  
Repeated Measures Anova ◽  
Ventral Tegmental

Background Dexmedetomidine induces a sedative response that is associated with rapid arousal. To elucidate the underlying mechanisms, the authors hypothesized that dexmedetomidine increases the activity of dopaminergic neurons in the ventral tegmental area, and that this action contributes to the unique sedative properties of dexmedetomidine. Methods Only male mice were used. The activity of ventral tegmental area dopamine neurons was measured by a genetically encoded Ca2+ indicator and patch-clamp recording. Dopamine neurotransmitter dynamics in the medial prefrontal cortex and nucleus accumbens were measured by a genetically encoded dopamine sensor. Ventral tegmental area dopamine neurons were inhibited or activated by a chemogenetic approach, and the depth of sedation was estimated by electroencephalography. Results Ca2+ signals in dopamine neurons in the ventral tegmental area increased after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 16.917 [14.882; 21.748], median [25%; 75%], vs. saline, –0.745 [–1.547; 0.359], normalized data, P = 0.001; n = 6 mice). Dopamine transmission increased in the medial prefrontal cortex after intraperitoneal injection of dexmedetomidine (40 μg/kg; dexmedetomidine, 10.812 [9.713; 15.104], median [25%; 75%], vs. saline, –0.498 [–0.664; –0.355], normalized data, P = 0.001; n = 6 mice) and in the nucleus accumbens (dexmedetomidine, 8.543 [7.135; 11.828], median [25%; 75%], vs. saline, –0.329 [–1.220; –0.047], normalized data, P = 0.001; n = 6 mice). Chemogenetic inhibition or activation of ventral tegmental area dopamine neurons increased or decreased slow waves, respectively, after intraperitoneal injection of dexmedetomidine (40 μg/kg; delta wave: two-way repeated measures ANOVA, F[2, 33] = 8.016, P = 0.002; n = 12 mice; theta wave: two-way repeated measures ANOVA, F[2, 33] = 22.800, P < 0.0001; n = 12 mice). Conclusions Dexmedetomidine activates dopamine neurons in the ventral tegmental area and increases dopamine concentrations in the related forebrain projection areas. This mechanism may explain rapid arousability upon dexmedetomidine sedation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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