Recruitment of inhibitory neuronal pathways regulating dopaminergic activity for the control of cocaine seeking.

Drug seeking is associated with the ventral tegmental area (VTA) dopaminergic (DA) activity. Previously, we have shown that brief optogenetic inhibition of VTA DA neurons with 1 s pulses delivered every 9 s attenuates cocaine seeking under extinction conditions in rats without producing overt signs of dysphoria or locomotor sedation. Whether recruitment of neuronal pathways inhibiting VTA neuronal activity would suppress drug seeking remains unknown.

Regulation of cocaine seeking behavior by locus coeruleus noradrenergic activity in the ventral tegmental area is time- and contingency-dependent.

Substance use disorder is linked to impairments in the ventral tegmental area (VTA) dopamine (DA) reward system. Noradrenergic (NA) inputs from locus coeruleus (LC) into VTA have been shown to modulate VTA neuronal activity, and are implicated in psychostimulant effects. Phasic LC activity controls time- and context-sensitive processes: decision making, cognitive flexibility, motivation and attention.

Alpha-adrenergic receptor blockade in the ventral tegmental area attenuates acquisition of cocaine-induced pavlovian associative learning.

Activity of the alpha-adrenergic receptor (α-AR) in the ventral tegmental area (VTA) modulates dopaminergic activity, implying its modulatory role in the behavioral functions of the dopamine (DA) system. Indeed, intra-VTA α-AR blockade attenuates conditioned stimulus dependent behaviors such as drug seeking responses signifying a role of the noradrenergic signaling in the VTA in conditioned behaviors. Importantly, the role of the VTA α-AR activity in Pavlovian associative learning with positive outcomes remains unknown.

Effects of brief inhibition of the ventral tegmental area dopamine neurons on the cocaine seeking during abstinence.

Preclinical studies strongly suggest that cocaine seeking depends on the neuronal activity of the ventral tegmental area (VTA) and phasic dopaminergic (DA) signaling. Notably, VTA pharmacological inactivation or dopamine receptor blockade in the forebrain may induce behavioral inhibition in general and acute aversive states in particular, thus reducing cocaine seeking indirectly. Such artifacts hinder successful translation of these findings in clinical studies and practice.

Alpha-adrenergic receptor blockade in the ventral tegmental area modulates conditional stimulus-induced cocaine seeking.

Exposure to drug-associated cues evokes drug-craving and upregulates noradrenaline (NA) and dopamine (DA) system activity. Importantly, conditional stimulus-induced drug-seeking behavior depends particularly on phasic DA signaling downstream from the ventral tegmental area (VTA), a midbrain structure key for the regulation of cocaine seeking. In particular, the activity of the alpha-adrenergic receptor (α-AR), which has recently been hypothesized to modulate salience encoding, is capable of bidirectional regulation of VTA dopaminergic activity.

Differential regulation of phasic dopamine release in the forebrain by the VTA noradrenergic receptor signaling.

Phasic dopamine (DA) release from the ventral tegmental area (VTA) into forebrain structures is implicated in associative learning and conditional stimulus (CS)-evoked behavioral responses. Mounting evidence points to noradrenaline signaling in the VTA as an important regulatory input. Accordingly, adrenergic receptor (AR) blockade in the VTA has been shown to modulate CS-dependent behaviors.

Noradrenergic and corticosteroid receptors regulate somatic and motivational symptoms of morphine withdrawal.

Somatic and motivational symptoms accompanying opiate withdrawal are considered one of the major reasons for relapse to opiate-seeking and opiate-taking behaviors. These symptoms are accompanied by the activation of stress-related processes including hypothalamic-pituitary-adrenal axis activity and noradrenergic (NA) signaling. In particular, the NA system plays an important role in the expression of somatic signs of opiate withdrawal, whereas glucocorticoid (GR) and mineralocorticoid receptors (MR) are activated during opiate abstinence.

Adrenergic Receptor Agonists' Modulation of Dopaminergic and Non-dopaminergic Neurons in the Ventral Tegmental Area.

The ventral tegmental area (VTA) neuronal population consists of dopaminergic (DAergic) and non-DAergic neurons (mainly GABAergic), the activity of which is intertwined with VTA behavioral functions. Both DAergic and GABAergic neurons in the VTA have been shown to express adrenergic receptors (ARs) and respond to AR stimulation. The aim of the present study was to demonstrate the effects of selective AR agonists on DAergic and non-DAergic neuronal activity in the central and lateral parts of the VTA using in vivo electrophysiological recording combined with microiontophoretic drug application in anaesthetized rats.

Noradrenergic signaling in the VTA modulates cocaine craving.

Exposure to drug-associated cues evokes drug-seeking behavior and is regarded as a major cause of relapse. Conditional stimulus upregulates noradrenaline (NA) system activity, but the drug-seeking behavior depends particularly on phasic dopamine signaling downstream from the ventral tegmental area (VTA). The VTA dopamine-ergic activity is regulated via the signaling of alpha -adrenergic and alpha -adrenergic receptors (α -ARs and α -ARs); thus, the impact of the conditional stimulus on drug-seeking behavior might involve NAergic signaling in the VTA.

Alpha-adrenergic receptor blockade in the VTA modulates fear memories and stress responses.

Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha-adrenergic receptor (α-AR) signaling in the VTA affects conditioned fear.

Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.

The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.