# Tonic and Phase Amoremetric Monitoring of Dopamine Using Microelectrode Arrays in Rat Striatum
## 3 Results
### Conformal MEAs for In Vivo Measures of DA from Multiple Recording Depths  
The proof-of-principle studies outlined above led us to design a novel 8-channel MEA with differential spacing of platinum recording site pairs to enable simultaneous measures of DA at multiple recording depths in the rat brain. The single-sided DSPR8 MEA was designed on earlier studies using S2 MEAs to measure DA. Figure 4A shows the 1-2 mm spacing between recording pairs on the DSPR8 MEA, which allows, in this case, one pair of sites to record in the primary motor cortex while the other three more ventral pairs (\(\geq\)2 mm from the cortical pair) are positioned to record at multiple depths in the dSTR (1 mm spacing between each pair in the dSTR). Once the tip of the DSPR8 MEA was lowered to the final DV coordinate, the electrochemical signals were allowed to reach a stable baseline (typically \(\geq\)90 min). Figure 4B-D show the self-referenced DA signal at each recording depth before and after systemic administration of the psychostimulant d-amphetamine (2 mg/kg, i.p.).  
Figure 3: Proof-of-concept for MEA-based measures of resting DA levels in vivo. (**A**) Reconstruction of differential cortical-striatal recording with a 4-channel S2 MEA. S2 MEAs were positioned in primary motor cortex and after establishing a baseline signal were lowered ventrally into the dSTR. (**B**) Baseline current differences measured in the anesthetized rat primary motor cortex and dSTR following self-referencing. Recording shows the cortical-striatal baseline current increase between the primary motor cortex (i.e., low DA innervation) and dSTR (i.e., high DA innervation). The difference between the baseline current measured in the dSTR vs. cortex represents resting DA levels. (**C**) The self-referenced cortical baseline was subtracted from the self-referenced baseline signal in dSTR to calculate differences in resting DA levels between the non-lesioned and 6-OHDA lesioned dSTR. ***\(p<0.001\), paired \(t\)-test. Note the low nanomolar detected levels of DA by the method. (**D**) High-performance liquid chromatography (HPLC) analysis of DA tissue content from non-lesioned and 6-OHDA lesioned dSTR. ***\(p<0.001\), paired \(t\)-test (n = 5–7).  
The onset of d-amphetamine changes in DA signaling was quite rapid. In vitro testing showed MEAs are insensitive to d-amphetamine.  
The effects of the psychostimulant, d-amphetamine, on DA release have been widely characterized and are a known way to measure non-calcium dependent release of DA [52]. Therefore, we assessed the effect of systemic administration of d-amphetamine (2 mg/kg, i.p.) on resting levels of DA in the anesthetized dSTR of rats. d-Amphetamine caused a rapid extracellular increase in DA. Interestingly, the elevated levels of resting DA were accompanied by DA transients seen more closely in Figure 5,  
Figure 4: Conformal MEA design for simultaneous measures of in vivo DA dynamics at multiple recording depths. (**A**) Depth profile illustrating location of each MEA pair, (**B–D**) concentration versus time plots for subjects 1–3 before and after administration of d-amphetamine (2 mg/kg, i.p.). Time axis bars are 10 min and concentration axis bars are 100 \(\upmu\)M.  
which are likely related to the complex actions of d-amphetamine on DA release. The number of spikes and the amplitudes varied in number and size (range: \(\sim\)5 nM to 800 nM). Of particular note is that this pilot study shows the variable response of DA nerve terminals to the d-amphetamine in subregions of the rat striatum and nucleus accumbens (ventral striatum) of the same animal.