The principal features and mechanisms of dopamine modulation in the prefrontal cortex

Nonvesicular release of neurotransmitter

Pharmacology and behavioral pharmacology of the mesocortical dopamine system

Microdialysis has become a frequently used method to study extracellular levels of GABA and glutamate in the central nervous system. However, the fact that the major part of GABA and glutamate as measured by microdialysis does not fulfill the classical criteria for exocytotic release questions the vesicular origin of the amino acids in dialysates. Glial metabolism or reversal of the (re)uptake sites has been suggested to be responsible for the pool of nonexocytotically released amino-acid transmitters that seem to predominate over the neuronal exocytotic pool. The origin of extracellular GABA and glutamate levels and, as a consequence, the implications of changes in these levels upon manipulations are therefore obscure. This review critically analyzes what microdialysis data signify, i.e., whether amino-acid neurotransmitters sampled by microdialysis represent synaptic release, carrier-mediated release, or glial metabolism. The basal levels of GABA and glutamate are virtually tetrodotoxin- and calcium-independent. Given the fact that evidence for nonexocytotic release mediated by reversal of the uptake sites as a release mechanism relevant for normal neurotransmission is so far limited to conditions of "excessive stimulation," basal levels most likely reflect a nonneuronal pool of amino acids. Extracellular GABA and glutamate concentrations can be enhanced by a wide variety of pharmacological and physiological manipulations. However, it is presently impossible to ascertain that the stimulated GABA and glutamate in dialysates are of neuronal origin. On the other hand, under certain stimulatory conditions, increases in amino-acid transmitters can be obtained in the presence of tetrodotoxin, again suggesting that aspecific factors not directly related to neurotransmission underlie these changes in extracellular levels. It is concluded that synaptic transmission of GABA and glutamate is strictly compartmentalized and as a result, these amino acids can hardly leak out of the synaptic cleft and reach the extracellular space where the dialysis probe samples.

Brain microdialysis of GABA and glutamate : What does it signify?

Carrier-mediated release of neurotransmitters

Calcium-independent release of amino acid neurotransmitters: fact or artifact?

Dopamine may influence striatal GABA release via three separate mechanisms

Release of endogenous GABA can occur through Ca2+-dependent and Ca2+-independent processes

Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca2+-deficient conditions in response to electrical field depolarization

Dopamine (DA) containing terminals of the nigrostriatal bundle make synaptic contacts with GABAergic cells.' However, there are contradictory findings regarding the impact of these afferents. Recently, there have been reports suggesting that DA can influence striatal y-aminobutyric acid (GABA) release through both DA receptor subtypes, the D 1 -mediated response being excitatory, and the D2 response being inhibitory.' Similar observations in the substantia nigra also have been reported.' Our investigations suggest that DA has a third effect on GABA efflux in the striatum, one that is not mediated through either type of receptor. Using slices from rat striatum we have observed that DA accelerates resting GABA efflux as well as electrically evoked GABA overflow through a process that is insensitive to D1 and D2 antagonists but can be blocked by nipecotic acid, an inhibitor of GABA ~ p t a k e . ~ In the current study, the impact of electrically and chemically released DA on [3H]GABA efflux from rat striatal slices was measured. Male, Sprague-Dawley rats, weighing 200-300 g, were used throughout these experiments. Animals were killed by decapitation, the brain was quickly removed, and coronal slices (350 pm) of the rostra1 part of the striatum were made. Slices were preincubated at 25OC in the presence of [3H]GABA (0.1 pM). After 60 minutes of preperfusion, 5-minute fractions were collected and analyzed for tritium by liquid scintillation spectroscopy. Slices were stimulated twice for 3 minutes using biphasic pulses (20 mA, 3-msecond pulse duration with 1-rnsecond delay, 10 Hz for 9 seconds). These stimulation periods coincided with the beginning of the third (S,) and twelfth (S,) 5-minute fractions. Spontaneous tritium efflux gradually decreased throughout the course of the

Effects of Endogenously Released Dopamine on [3H]γ‐Aminobutyric Acid Efflux from Rat Striatal Slices

Sandor Bernath

Papers

Calcium-independent release of amino acid neurotransmitters: fact or artifact?

Dopamine may influence striatal GABA release via three separate mechanisms

Release of endogenous GABA can occur through Ca2+-dependent and Ca2+-independent processes

Na+ influx through Ca2+ channels can promote striatal GABA efflux in Ca2+-deficient conditions in response to electrical field depolarization

Effects of Endogenously Released Dopamine on [3H]γ‐Aminobutyric Acid Efflux from Rat Striatal Slices