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VTA-specific noradrenergic regulation of motivational control

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Insight into motivational control

Acquired behaviour is motivated by incentive learning. The molecular determinants of this process constitute an active field of investigation.

Fundamental Research
Health

Deciding on a course of action usually entails evaluation of its consequences and those of various alternative actions. This adaptive behaviour is driven by motivational control and its malfunction may lead to addiction. The neurotransmitter dopamine (DA) acts as a precursor to the noradrenaline (NA) system and plays a crucial role in the rewards system and positive motivation. However, its exact contribution to motivational control is not fully understood. The EU-funded VTANORREGMOTCONTROL project evaluated the role of the NA system in motivational control in a mouse model of opiate exposure. In this behavioural model of motivational control, scientists employed real-time dynamic optical stimulation of NA neurons to investigate the implicated mechanisms. In addition, they worked towards identifying the brain loci within the NA system that are responsible for a specific type of motivational control. Results demonstrated that NA signalling in the midbrain ventral tegmental area (VTA), arising from the phasic activity of the solitary nucleus NTS, regulates cocaine-induced associative learning. Scientists examined the background activity known as tonic firing as well as the pre-synaptic (phasic) stimulation of NA neurons. They observed that neither tonic nor phasic stimulation originating in the part of the brain known as locus coeruleus (LC) had any reinforcing or aversive effects. Furthermore, the project demonstrated that NTS NA signalling in the VTA regulates anxiety-like behaviour. Further experimentation in the cocaine mouse model of learning and anxiety indicated a role for VTA NA signalling. This was attributed to alpha1-adrenergic receptors leading to decreased DA and increased non-DA VTA neuronal activity. In conclusion, the VTANORREGMOTCONTROL study provided important knowledge on the mechanisms that govern anxiety and DA-mediated associative learning. The findings underscored the importance of the network between DA and distinct brain regions in regulating motivational control. From a clinical perspective, this information brings the scientific community a step closer to comprehending addiction and finding targeted approaches to tackle it.

Keywords

Motivational control, dopamine, noradrenaline system, VTANORREGMOTCONTROL, ventral tegmental area

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