Regional Variation in Striatal Dopamine Spillover and Release Plasticity.

Recent optical observations of dopamine at axon terminals and kinetic modeling of evoked dopamine responses measured by fast scan cyclic voltammetry (FSCV) support local restriction of dopamine diffusion at synaptic release sites. Yet, how this diffusion barrier affects synaptic and volume transmission is unknown. Here, a deficiency in a previous kinetic model's fitting of stimulus trains is remedied by replacing an earlier assumption that dopamine transporters (DATs) are present only on the outer side of the diffusion barrier with the assumption that they are present on both sides.

Vesicular Antipsychotic Drug Release Evokes an Extra Phase of Dopamine Transmission.

Many psychiatric drugs are weak bases that accumulate in and are released from synaptic vesicles, but the functional impact of vesicular drug release is largely unknown. Here, we examine the effect of vesicular release of the anxiolytic antipsychotic drug cyamemazine on electrically evoked striatal dopamine responses with fast scan cyclic voltammetry. Remarkably, in the presence of nanomolar extracellular cyamemazine, vesicular cyamemazine release in the brain slice can increase dopamine responses 30-fold.

Kinetic Diversity of Striatal Dopamine: Evidence from a Novel Protocol for Voltammetry.

In vivo voltammetry reveals substantial diversity of dopamine kinetics in the rat striatum. To substantiate this kinetic diversity, we evaluate the temporal distortion of dopamine measurements arising from the diffusion-limited adsorption of dopamine to voltammetric microelectrodes. We validate two mathematical procedures for correcting adsorptive distortion, both of which substantiate that dopamine's apparent kinetic diversity is not an adsorption artifact.

Modeling the kinetic diversity of dopamine in the dorsal striatum.

Dopamine is an important neurotransmitter that exhibits numerous functions in the healthy, injured, and diseased brain. Fast scan cyclic voltammetry paired with electrical stimulation of dopamine axons is a popular and powerful method for investigating the dynamics of dopamine in the extracellular space. Evidence now suggests that the heterogeneity of electrically evoked dopamine responses reflects the inherent kinetic diversity of dopamine systems, which might contribute to their diversity of physiological function.

Kinetic diversity of dopamine transmission in the dorsal striatum.

Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat.

A novel restricted diffusion model of evoked dopamine.

In vivo fast-scan cyclic voltammetry provides high-fidelity recordings of electrically evoked dopamine release in the rat striatum. The evoked responses are suitable targets for numerical modeling because the frequency and duration of the stimulus are exactly known. Responses recorded in the dorsal and ventral striatum of the rat do not bear out the predictions of a numerical model that assumes the presence of a diffusion gap interposed between the recording electrode and nearby dopamine terminals.

Region- and domain-dependent action of nomifensine.

The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast-scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain-dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked DA overflow in the slow domains compared with the fast domains.