https://numerons.files.wordpress.com/2012/04/11-stressor-controllability-and-learned-helplessness.pdf

Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor.

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?

There is evidence for stressor- and brain region-specific selectivity in serotonergic transmission responses to aversive stimuli. The aim of the present review is to provide an overview of the effects of different acute and repeated/chronic stressors on serotonin (5-HT) release and reuptake, extracellular 5-HT levels, and 5-HT pre- and postsynaptic receptors in areas tightly linked to the control of fear and anxiety, namely the dorsal and median raphe nuclei, the frontal cortex, the amygdala and the hippocampus. In addition, our knowledge of the impacts of corticoids on serotonergic systems in these brain areas is also briefly provided to examine whether the hypothalamo-pituitary-adrenal axis may play a role in stress-induced alterations in 5-HT neurotransmission. Taken together, the data presented reinforce the hypothesis that stress affects such a transmission, partly through the actions of corticoids. However, we are still left with unanswered, albeit crucial questions. First, the question of the specificity of the serotonergic responses to stress, with regard to the site of action and the nature of the stressor still remains open due to the heterogeneity of the results obtained so far. This could indicate that environmental factors, other than the stressor itself, may have enduring consequences on 5-HT sensitivity to stress. Second, the question regarding the role of stress-elicited changes in 5-HT transmission within coping processes finds in most cases no clearcut answer. In keeping with human symptomatology, the need to consider the environment (including the early one) and the genetic status when assessing the effects of stress on 5-HT neurotransmission is underlined. Such a consideration could help to answer the questions raised.

Serotonin, stress and corticoids.

Origin and functional role of the extracellular serotonin in the midbrain raphe nuclei.

5-Hydroxytryptamine 2C Receptors in the Basolateral Amygdala Are Involved in the Expression of Anxiety After Uncontrollable Traumatic Stress

Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphe and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1μM and 10μM) into the dorsal raphe simultaneously decreased dorsal raphe and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10μM), hippocampal 5-HT release was profoundly reduced but dorsal raphe 5-HT remained unchanged.

F. F. Matos

Papers

Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: raphé control of somatodendritic and terminal 5-HT release.