Hypofunction of the mesolimbic dopamine system will impair the function of the mesocortical and nigrostriatal dopamine systems by influencing dopamine release and the cortico-striato-thalamo-cortical circuits that dopamine modulates.
It would be great if the authors could address this point, and one way might be to determine whether GAT-1 inhibition influences dopamine release measured by voltammetry-GABA corelease by many terminals should have some effect on total dopamine release, but involvement of only a subset would produce minimal if any effect.
Several animal and human studies have demonstrated that the frontal cortex exerts an important influence on striatal dopamine release both through the modulation of dopaminergic neuronal firing [6] [7] and a direct effect on nerve terminals [8] [14].
Given that adaptive gain theory predicts that low tonic, rather than high tonic, LC-NE activity should characterize motivated performance (i.e., enhanced task engagement), this pattern of pupil activity may reflect other possible influences (i.e., reward-related dopamine release) in addition to LC-NE system activity.
Lecourtier, L., Defrancesco, A. & Moghaddam, B. Differential tonic influence of lateral habenula on prefrontal cortex and nucleus accumbens dopamine release.
Although the research had emphasized the beneficial influences of dopamine, behavioral data provided the first indication that high levels of dopamine release, such as occurs during stress exposure (Deutch and Roth 1990), could be detrimental to dlPFC function through excessive stimulation of D1 receptors (Arnsten and Goldman-Rakic 1990 , 1998 Arnsten et al. 1994; Murphy et al. 1996; Arnsten 1998).
In animal models, it is well established that activation of reward pathways provides both a strong influence on food choice [29], [30] and feeding behavior [31], associated with an increase in dopamine release in the NAc [32].
Evaluation of dopamine receptors is not only important at the site of release such as the NAcc but also in the VTA as because of dendritic dopamine release (Cragg & Greenfield 1997), it is likely that it acts locally to influence reward motivated behaviors.
Nicotine involves dopamine release, which is key in signaling pleasure.
Pregnenolone sulfate increases dopamine release in the rat striatum.
