Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine-lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.dopamine | voltammetry | synchrony | nucleus accumbens | dorsal striatum D opamine neurotransmission modulates arousal and motivation, and is important to the expression of reward-seeking behavior. Dopamine is released on a subsecond timescale during unexpected reward (1, 2), and becomes time-locked to cues that predict reward (3-7). Dopamine transients in the nucleus accumbens (NAc) occur as a result of cell firing in the ventral tegmental area (VTA) (8, 9), and in rats reach concentrations of 50-200 nM before returning to baseline (10, 11). Striatal dopamine transients also occur spontaneously during periods of rest (10, 11), reflecting endogenous dopamine modulation. The magnitude and frequency of dopamine transients increase in response to drugs of abuse (12, 13), which is thought to contribute to their reinforcing properties (14). Although numerous studies have summarized the function of dopamine circuits in reward-based behaviors (15, 16) and motor control (17-19), anatomic descriptions of dopamine projections are conflicting (20-23). Recent evidence suggests that some dopamine neurons project contralateral to their origin (22, 23), contradictory to the uncrossed dopamine system described previously (20, 21). To date, the significance of contralaterally projecting dopamine neurons, and how they may contribute to cross-hemispheric signaling, have not been established.A potential role for contralateral dopamine projections emerged in a recent study on brain stimulation reward (24). When rats were trained to self-stimulate the VTA, infusion of dopamine receptor antagonists in the NAc suppressed stimulation. This effect was seen whether the infusion was contralateral or ipsilateral to the stimulation site, reflecting cross-hemispheric modulation of the behavior. Furthe...

Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in the water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors.

Using fast‐scan cyclic voltammetry paired with pharmacology, the authors show that infralimbic catecholamine release following locus coeruleus stimulation is noradrenergic, but not dopaminergic, and not affected by acute ethanol. With previous work, these data suggest differential effects of ethanol on prefrontal norepinephrine and dopamine, a region important in addiction‐related pathways.

Activity in the mesolimbic dopamine (DA) pathway is known to have a role in reward processing and related behaviors. The mesolimbic DA response to reward has been well-examined, while the response to aversive or negative stimuli has been studied to a lesser extent and produced inconclusive results. However, a brief increase in the DA concentration in terminals during nociceptive activation has become an established but not well-characterized phenomenon. Consequently, the interpretation of the significance of this neurochemical response is still elusive. The present study was designed to further explore these increases in subsecond DA dynamics triggered by negative stimuli using voltammetry in anesthetized rats. Our experiments revealed that repeated exposure to a tail pinch resulted in more efficacious DA release in rat nucleus accumbens. This fact may suggest a protective nature of immediate DA efflux. Furthermore, a sensitized DA response to a neutral stimulus, such as a touch, was discovered following several noxious pinches, while a touch applied before these pinches did not trigger DA release. Finally, it was found that the pinch-evoked DA efflux was significantly decreased by ethanol acutely administrated at an analgesic dose. Taken together, these results support the hypothesis that subsecond DA release in the nucleus accumbens may serve as an endogenous antinociceptive signal.

In this study we demonstrate what kind of relative alterations can be expected in average perfusion and blood flow oscillations during postural changes being measured in the skin of limbs and on the brow of the forehead by wearable laser Doppler flowmetry (LDF) sensors. The aims of the study were to evaluate the dynamics of cutaneous blood perfusion and the regulatory mechanisms of blood microcirculation in the areas of interest, and evaluate the possible significance of those effects for the diagnostics based on blood perfusion monitoring. The study involved 10 conditionally healthy volunteers (44 ± 12 years). Wearable laser Doppler flowmetry monitors were fixed at six points on the body: two devices were fixed on the forehead, on the brow; two were on the distal thirds of the right and left forearms; and two were on the distal thirds of the right and left lower legs. The protocol was used to record three body positions on the tilt table for orthostatic test for each volunteer in the following sequence: (a) supine body position; (b) upright body position (+75°); (c) tilted with the feet elevated above the head and the inclination of body axis of 15° (−15°, Trendelenburg position). Skin blood perfusion was recorded for 10 min in each body position, followed by the amplitude–frequency analysis of the registered signals using wavelet decomposition. The measurements were supplemented with the blood pressure and heart rate for every body position analysed. The results identified a statistically significant transformation in microcirculation parameters of the average level of skin blood perfusion and oscillations of amplitudes of neurogenic, myogenic and cardiac sensors caused by the postural changes. In paper, we present the analysis of microcirculation in the skin of the forehead, which for the first time was carried out in various positions of the body. The area is supplied by the internal carotid artery system and can be of particular interest for evaluation of the sufficiency of blood supply for the brain.

The article describes a multiparametric approach to the assessment of cutaneous microcirculation in dermatological patients (using the example of psoriasis patients). The multiparametric diagnostic approach consisted of three stages of successive measurements performed according to the methodology of laser speckle contrast imaging (LSCI), laser Doppler flowmetry (LDF), and videocapillaroscopy (VCS). Experimental studies on hemodynamic parameters were conducted in psoriatic patients with a course of conservative treatment. A combined application of optical noninvasive diagnostic methods allowed physicians to record changes taking place in the microcirculatory bed during treatment. It has been found that microcirculatory disorders observed before the start of treatment in the field of psoriatic plaques (an increase in the density of the capillary network, an increase in the indicator of microcirculation, nutritive blood flow and the amplitudes of myogenic and cardiac oscillations) were normalized due to the applied treatment, on which the assessment of its efficacy may be based. The suggested approach may be used for diagnosing microcirculatory disorders emerging in psoriasis in its preclinical stage, as well as for developing and testing new pharmacological means for its treatment.

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