Inhibition of stimulated dopamine release and hemodynamic response in the brain through electrical stimulation of rat forepaw

Abstract

The subcortical response to peripheral somatosensory stimulation is not well studied. Prior literature suggests that somatosensory stimulation can affect dopaminergic tone. We studied the effects of electrical stimulation near the median nerve on the response to an amphetamine induced increase in synaptic dopamine. We applied the electrical stimulation close to the median nerve 20 minutes after administration of 3mg/kg amphetamine. We used fMRI and microdialysis to measure markers of DA release, together with the release of associated neurotransmitters of striatal Glutamate (Glu) and GABA.Result-1) Changes in cerebral blood volume (CBV), a marker used in fMRI, indicate that electrical stimulation significantly attenuated increased DA release (due to AMPH) in the striatum, thalamus, medial prefrontal and cingulate cortices. 2) Microdialysis showed that electrical stimulation increased Glu and GABA release and attenuated the AMPH-enhanced DA release. The striatal DA dynamics correlated with the CBV response.Conclusion-These results demonstrate that electrical stimulation near the median nerve activates Glu/GABA release which subsequently attenuate excess striatal DA release. These data provide evidence for physiologic modulation caused by electroacupuncture at points near the median nerve.

Baseline GABA concentration and fMRI response

“…A negative correlation between BOLD response and GABA, and between VASO-CBV response and GABA was observed as hypothesized, and related findings have been observed previously using fMRI and contrast agent based techniques (Chen et al, 2008;Reese et al, 2002). However, the observed positive correlation between CBFweighted ASL and baseline GABA was contrary to our hypothesis, and to some previously published results of CBF measurements using different approaches (Reese et al, 2002;Roland and Friberg, 1988;Spanaki et al, 1999).…”

Restoring cerebral dopamine homeostasis by electrical forepaw stimulation: An FMRI study

“…Since the approach of facilitating basal ganglia feedback loop through peripheral stimulation relies on the self-adjusting mechanism intrinsic to the basal ganglia loop, the adjustment theoretically can be applied to disorder conditions with either excessive DA (such as in addiction) or with deficient DA innervations (such as in PD). Indeed, such a phenomenon of bidirectional adjustment by EFS is supported by combining data present here for the DA deficient condition and the data published in (Chen et al, 2008a; Chen et al, 2008b) for the DA excessive condition. Interestingly, the effect of EFS on the depressed DA condition appeared to last for the duration of EFS in the quinpirole experiment, but was transient in the Parkinsonian experiment (Figure 4).…”

“…We previously demonstrated that innocuous EFS (1mA at 2Hz or 100Hz) effectively attenuated excessive DA concentration in the striatum (Chen et al, 2008a; Chen et al, 2008b). The excessive DA condition was induced pharmacologically by D-amphetamine, a robust DA releaser.…”

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

“…However, from the correlations in our study we cannot ascertain the direction of the association; so we cannot determine if the association with D2 receptors reflects DA's modulation of the somatosensory cortex and/or the influence of the somatosensory cortex on striatal D2 receptor availability. Indeed there is ample evidence that the somatosensory cortex influences brain DA activity including striatal DA release (Huttunen et al, 2003;Rossini et al, 1995;Chen et al, 2007). There is also evidence that DA modulates the somatosensory cortex in the human brain (Kuo et al, 2007).…”