In vivo measurement of somatodendritic release of dopamine in the ventral tegmental area

Abstract

The ventral tegmental area (VTA), the locus of mesolimbic dopamine cell bodies, contains dopamine. Experiments in brain slices have demonstrated that VTA dopamine can be released by local electrical stimulation. Measurements with both push-pull cannula and microdialysis in intact animals have also obtained evidence for releasable dopamine. Here we demonstrate that dopamine release in the VTA can be evoked by remote stimulations of the medial forebrain bundle (MFB) in the anesthetized rat. In initial experiments, the MFB was electrically stimulated while a carbon-fiber electrode was lowered to the VTA, with recording by fast-scan cyclic voltammetry. While release was not observed with the carbon fiber 4 to 6 mm below dura, a voltammetric response was observed a t 6-8 mm below dura, but the voltammogram was poorly defined. At lower depths, in the VTA, dopamine release was evoked. Immunohistochemistry experiments with antibodies for tyrosine hydroxylase (TH) confirmed that dopamine processes were primarily found below 8 mm. Similarly, tissue content determined by liquid chromatography revealed serotonin but not dopamine dorsal to 8 mm with both dopamine and serotonin at lower depths. Evaluation of the VTA signal by pharmacological means showed that it increased with inhibitors of dopamine uptake, but release was not altered by D2 agents. Dopamine release in the VTA was frequency dependent and could be exhausted by stimulations longer than 5 s. Thus, VTA dopamine release can be evoked in vivo by remote stimulations and it resembles release in terminal regions, possessing a similar uptake mechanism and a finite releasable storage pool.

In vivo electrochemical evidence for simultaneous 5‐HT and histamine release in the rat substantia nigra pars reticulata following medial forebrain bundle stimulation

“…While the second substrate overlaps with the voltammograms for 5‐HT, it does not interfere with the concentration of 5‐HT obtained at 0.65 V because its electrolysis peaks occur later in the cyclic voltammogram. We have previously found somatodendritic dopamine release in the ventral tegmental area upon MFB stimulation (Kita et al. 2009), however, because of the low levels of dopamine in the SNR (Heeringa and Abercrombie 1995) and the low sensitivity of the 5‐HT specific waveform to dopamine (Hashemi et al.…”

“…1986) that is located in the medial forebrain bundle (MFB). We previously showed that electrical stimulation of the MFB released an unidentified substance in the red nucleus of the rat that we suspected was 5‐HT (Kita et al. 2009).…”

Dynamic regulation of midbrain dopamine neuron activity: intrinsic, synaptic, and plasticity mechanisms

“…Vesicular monoamine transporter 2 (VMAT2)-positive vesicles, which would underlie Ca 2+ -dependent vesicular DA release from the somoatodendritic area (Rice et al, 1997, Chen and Rice, 2001, Kita et al, 2009), have also been detected in DA neuron dendrites (Nirenberg et al, 1996). Released DA exerts feedback inhibition of DA neuron activity via activation of D2 autoreceptors, causing GIRK-mediated hyperpolarization (Groves et al, 1975, Lacey et al, 1987).…”

Ethanol Action on Dopaminergic Neurons in the Ventral Tegmental Area

“…Vesicular monoamine transporter 2 (VMAT2)-positive vesicles, which would underlie Ca 2+ -dependent vesicular DA release from the somoatodendritic area (Chen and Rice, 2001; Kita et al ., 2009; Rice et al ., 1997), have also been detected in DA neuron dendrites (Nirenberg et al ., 1996). Released DA exerts feedback inhibition of DA neuron activity via activation of D2 autoreceptors causing GIRK-mediated hyperpolarization (Groves et al ., 1975; Lacey et al ., 1987).…”