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A push-pull cannula supplied with artificial CSF was implanted in the striatum of anaesthetized rats, and the basal extracellular DA and DOPAC was assayed in the superfusates using HPLC and electrochemical detection. Simultaneously, a carbon fibre electrode was implanted in close proximity of the cannula and the evoked DA release was detected by differential pulse amperometry during stimulation of the DA axons. Local treatments with cadmium (100 μM) blocked the evoked DA release (−90%), but substantially increased the basal extracellular DA (+ 125%). The effects of glutamate agonists NMDA (1 mM) and kainate (0.1 mM), known to increase basal extracellular DA were confirmed (+150% and +60% respectively). It was, however, simultaneously observed that the evoked DA release was inhibited (−80% and −50%, respectively). Amphetamine (1 μM) released DA (+150%) and produced also an increase (+100%) of the evoked DA release. These results, apparently conflicting, show that the two mechanisms releasing dopamine (firing-dependent and not) can be directly and simultaneously observed. These two releasing processes appear to be not strictly antagonist. They are also differently and independently modulated by calcium and by local influences such those conveyed by glutamate.

Rats were anesthetized with fluothane and implanted in the caudate nucleus with a push-pull cannula supplied with artificial CSF containing the tritiated precursor of dopamine (DA), [3H]tyrosine. Total DA and dihydroxyphenylacetic acid (DOPAC) were measured in successive 20 min fractions using high performance liquid chromatography and electrochemical detection. Radioisotopic counting of the peaks permitted the calculation of the specific activity of both DA and DOPAC released into the extracellular space. Local applications of potassium (8, 16 and 32 mM) induced a dose-dependent increase of the release of DA with a decrease of its specific activity as evidence of the involvement of a stored DA pool. Base release of DOPAC was increased by repeating potassium applications with a temporary decrease during the applications. Superfusion with alpha-methyl-p-tyrosine produced a decrease of both the [3H]DA and total DA with a simultaneous decrease of its specific activity. This decrease was considered to be an indicator of the involvement by synthesis inhibition of the stored amine, but the simultaneous decrease of the specific activity of DOPAC suggests that this release was intraterminal. These results constitute the first direct observation that DA terminals act with two separate pools (stored and releasable) and suggest that the stored amine is preferentially released intraterminally. Systemic injection of reserpine induced a decrease of the release of DA and DOPAC without alteration of DA-specific activity when the specific activity of DOPAC was lowered. From these results it is concluded that the releasable compartment of the amine is located, in part, in vesicles different in nature from the vesicles containing the stored amine.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to study the mechanisms regulating the dopaminergic nigroamygdaloid cells, the release of dopamine was observed in the central nucleus of the amygdaloid complex. Halothane anesthetized rats were implanted, according to the experiment, with one or two push-pull cannulae in the central nuclei of the amygdala (ACE), the substantia nigra (SN) and/or the caudate nucleus (CN). Cannulae were supplied with artificial cerebrospinal fluid (CSF) containing tritiated tyrosine, and labeled dopamine [3H]DA was evaluated in successive superfusate fractions. Electrical stimulation of the medial forebrain bundle with an implanted bipolar electrode induced an increase of the [3H]DA release in the ipsi- and contralateral ACE. Electrical stimulation of the SN produced only a very delayed effect in the ipsilateral ACE but an immediate and large increase of [3H]DA release in the contralateral structure. Superfusion of unlabeled DA and α-methyl-p-tyrosine in the SN remained ineffective on the [3H]DA release in the ipsilateral ACE. In this structure the release of [3H]DA was, however, decreased by nigral superfusion with γ-amino-butyric acid (GABA). d -(+)-Amphetamine (1 μM), when superfused in the CN, induced a large enhancement of the [3H]DA release in the ipsilateral ACE simultaneously with the local increase of [3H]DA release. The results presented here are in agreement with the previous studies concerning the anatomical organization of the dopaminergic nigroamygdaloid pathway. The DA cell bodies located in the SN appear insensitive to a local action of DA, perhaps due to a lack of autoreceptors. They are, however, powerfully inhibited by GABA and the relation observed between the [3H]DA release in the CN and ACE support the hypothesis that the SN can act as a relay between the extrapyramidal and limbic systems.

The release of dopamine in the substantia nigra and striatum was investigated in halothane anaesthetized rats by means of the pushpull cannula method. Electrical stimulation of the subthalamic nucleus produced a marked enhancement of dopamine release in the ipsilateral substantia nigra. This effect is likely to be mediated by subthalamic efferent neurons since the application of acetylcholine in the subthalamic nucleus produced a similar effect. A later decrease of dopamine release was always observed in the ipsilateral striatum and was attributed to the autoregulation mechanisms of nigro-striatal dopaminergic neurons.

The nucleus centralis of the amygdaloid complex was examined for the localization of the release of newly synthesized dopamine. Results are in good agreement with histochemical descriptions. The functional role of this release remains to be established.