Inhibitory effect of galanin on dopamine induced increased oxytocin secretion in rat neurohypophyseal tissue cultures

The regulation of oxytocin (OT) release by galanin (GAL) at the neurohypophyseal (NH) nerve terminal is not adequately understood. The effect of GAL on the secretion of OT was studied in 13- to 14-day cultures of isolated rat NH tissue. By this time, the hormone content of the medium had become constant. The OT content of the supernatant medium was determined by RIA after a 1- or 2-h incubation. A significantly decreased content of OT was found following incubation with 10(-6)-10(-8) M doses of GAL. Dopamine (DA) and the DA-active drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased the OT synthesis of NH tissue cultures. This elevation of OT secretion could be blocked by the administration of GAL together with DA, APM or PLG. The DA-blocking effect of GAL was prevented by previous treatment with the GAL receptor antagonist galantid (M15). The results indicate that OT release from the NH is directly influenced by the GAL-ergic system. The GAL-ergic control of OT secretion from NH tissue in rats can occur at the level of the posterior pituitary.     

Inhibitory effect of galanin on dopamine-induced enhanced vasopressin secretion in rat neurohypophyseal tissue cultures

The effect of galanin (GAL) on vasopressin (VP) secretion was studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP content of the supernatant was determined by radioimmunoassay (RIA) after a 1- or 2-h incubation. A significantly decreased content of VP was detected following the administration of 10(-6)-10(-9) M doses of GAL. Dopamine (DA) and the DA-active drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased the VP level of NH tissue cultures. This VP concentration elevation could be blocked by the administration of GAL together with DA, APM or PLG. The DA-blocking effect of GAL was prevented by previous treatment with the GAL receptor antagonist galantid (M15). The results indicate that VP release is directly influenced by the GAL-ergic system. The GAL-ergic control of VP secretion from NH tissue in rats can occur independently of the hypothalamus, at the level of the posterior pituitary.     

Serotonin-induced enhancement of vasopressin and oxytocin secretion in rat neurohypophyseal tissue culture

The effects of serotonin (5-hydroxytryptamine; 5-HT) on vasopressin (VP) and oxytocin (OT) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP and OT contents of the supernatant were determined by radioimmunoassay after a 1 or 2 h incubation. Significantly increased levels of VP and OT production were detected in the tissue culture media following 5-HT administration, depending on the 5-HT dose. The elevation of NH hormone secretion could be partially blocked by previous administration of the 5-HT antagonist ketanserin or metergoline. WAY-100635 did not influence the increased VP secretion induced by 5-HT, but the elevated OT production was prevented by WAY-100635 before 5-HT administration. The application of WAY-100635, ketanserin or metergoline, after 5-HT administration proved ineffective. The results indicate that NH hormone release is influenced directly by the serotonergic system. The serotonergic control of VP and OT secretion from the NH tissue in rats can occur at the level of the posterior pituitary.     

Histamine-induced enhancement of vasopressin and oxytocin secretion in rat neurohypophyseal tissue cultures

The effects of histamine (HA) on vasopressin (VP) and oxytocin (OT) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP and OT contents of the supernatant were determined by radioimmunoassay (RIA) after a 1 or 2-h incubation. Significantly increased levels of VP and OT production were detected in the tissue culture media following HA administration, depending on the HA dose. The elevation of NH hormone secretion could be partially blocked by previous administration of the HA antagonist mepyramine (MEP, an H1 receptor antagonist) or cimetidine (CIM, an H2 receptor antagonist). Thioperamide (TPE, an H3-H4 receptor antagonist) did not influence the VP or OT secretion increase induced by HA. The application of MEP, CIM or TPE after HA administration proved ineffective. The H1 and H2 receptors are mainly involved in the HA-induced increase of both VP and OT secretion in isolated NH tissue cultures. The results indicate that NH hormone release is influenced directly by the histaminergic system, and the histaminergic control of VP and OT secretion from the NH tissue in rats can occur at the level of the posterior pituitary.     

Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release

The supraoptic nuclei are innervated by the A1 neurons of the caudal ventrolateral medulla. Substances colocalized in the A1 terminals include norepinephrine (NE), substance P (SP), ATP, and neuropeptide Y (NPY). ATP, acting at P(2x) receptors, caused rapid and unsustained stimulation of vasopressin (VP) and oxytocin (OT) release from perifused explants of the hypothalamo-neurohypophysial system. SP elicited a concentration-dependent stimulation of VP and OT release that was large and sustained compared with other stimuli. ATP, but not phenylephrine (PE, alpha(1)-adrenergic agonist), augmented the response to SP (1 microM). In contrast, NPY did not alter basal nor ATP-induced VP or OT release, but it did cause sustained potentiation of PE-induced VP and OT release. The Y(1)-agonist, [Leu(31),Pro(34)]-NPY, increased VP and OT release, suggesting that the ineffectiveness of NPY reflects opposing actions at pre- and postsynaptic receptors. However, [Leu(31),Pro(34)]-NPY did not potentiate hormone responses to ATP or PE. The differential responses to these colocalized neurotransmitters and neuropeptides illustrate the range of potential responses that stimulation of this pathway might elicit from supraoptic neurons.     

Significance of the adrenergic system in the regulation of vasopressin secretion in rat neurohypophyseal tissue cultures

The effects of adrenaline (A) and noradrenaline (NA) on vasopressin (VP) secretion were studied in 13-14-day cultures of isolated rat neurohypophyseal (NH) tissue. The VP contents of the supernatant media were determined by radioimmunoassay after a 1 or 2-h incubation. Significantly increased VP levels were detected in the tissue culture media following the administration of A (an alpha+beta(2)-receptor agonist), depending on the dose of A. The VP secretion elevation was totally blocked by the previous administration of phentolamine (an alpha(1)+alpha(2)-receptor antagonist) or corynanthine (an alpha(1)-receptor antagonist). Yohimbine (an alpha(2)-receptor antagonist) did not influence the VP secretion increase induced by A. After the administration of NA (a beta+alpha(1)-receptor agonist), a VP secretion elevation was again detected, but the degree of enhancement proved smaller than that of the VP secretion increase induced by A. Propranolol (a beta(1)+beta(2)-receptor antagonist) before NA administration prevented the VP secretion increase. Atenolol (a beta(1)-receptor antagonist) did not block the VP secretion elevation induced by NA. Corynanthine (an alpha(1)-receptor antagonist) treatment before NA administration reduced the NA-induced VP enhancement, because NA has an alpha(1)-receptor agonist character in addition to its main character (a beta-receptor agonist). Surprisingly, the administration of pindolol (a beta(1)+beta(2)-receptor antagonist) enhanced VP secretion. This contradictory effect can be explained in that pindolol not only acts as a blocker, but also exerts "intrinsic sympathomimetic action" and a strong adrenergic agonist effect. Pindolol before NA administration significantly increased the NA-induced VP elevation. CONCLUSIONS: Mainly the alpha(1)- and beta(2)-adrenergic receptors are involved in the A- or NA-induced increase of VP secretion in isolated NH tissue cultures. The results indicate that VP release is influenced directly by the adrenergic system, and the adrenergic control of VP secretion from the NH tissue in rats can occur at the level of the posterior pituitary.     

Tachykinin neurokinin 3 receptor signaling in cholecystokinin-elicited release of oxytocin and vasopressin

Neurokinin 3 receptor (NK3R) signaling has an integral role in the stimulated oxytocin (OT) and vasopressin (VP) release in response to hyperosmolarity and hypotension. Peripheral injections of cholecystokinin (CCK) receptor agonists for the CCK-A (sulfated CCK-8) and CCK-B (nonsulfated CCK-8) receptors elicit an OT release in rat. It is unknown whether NK3R contributes to this endocrine response. Freely behaving male rats were administered an intraventricular pretreatment of 250 or 500 pmol of SB-222200, a specific NK3R antagonist, or 0.15 M NaCl before an intraperitoneal or intravenous injection of CCK-8 (nonsulfated or sulfated) or 0.15 M NaCl. Blood samples were taken before intraventricular treatment and 15 min after intraperitoneal or intravenous injection, and plasma samples were assayed for OT and VP concentration. Intraperitoneal injection of both nonsulfated and sulfated CCK-8 significantly increased plasma OT levels and had no effect on plasma VP levels. Intravenous injection of sulfated CCK-8 stimulated an increase in plasma OT levels and did not alter plasma VP levels. However, intravenous injection of nonsulfated CCK-8 stimulated a significant increase in plasma levels of both OT and VP. No other studies have demonstrated CCK-8-stimulated release of VP in rat. NK3R antagonist did not alter baseline levels of either hormone. However, pretreatment of NK3R antagonist significantly blocked the CCK-stimulated release of OT in all CCK treatment groups and blocked VP release in response to intravenous injection of nonsulfated CCK-8. Therefore, central NK3R signaling is required for OT and VP release in response to CCK administration.     

Expression of the enzymes of dopamine synthesis in non-dopaminergic neurons: functional significance and regulation

Dopamine(DA), the most widely distributed in the nervous system and functionally important chemical signal, is synthesized in DA-ergic neurons from L-tyrosine by means of two enzymes, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). Apart from the enzymes, specific DA transporter is an attribute of DA-ergic neurons. In the mid eighties of the last century, in addition to DA-ergic neurons, those expressing only one enzyme, TH or AADC, have been discovered. These "monoenzymatic" neurons occurred to be more numerous and more widely distributed in the brain compared to DA-ergic neurons that manifests their wide involvement to the brain functioning. It has been demonstrated that the monoenzymatic neurons expressing complementary enzymes of DA synthesis produce this neurotransmitter in cooperation. In this case, L-tyrosine is transformed to L-DOPA in TH containing neurons that is followed by L-DOPA release and uptake from the intercellular space to AADC containing neurons for DA synthesis. Moreover, the L-DOPA uptake to DA-ergic or serotoninergic neurons results either in the increase or the onset of DA synthesis in addition to serotonin, respectively. The expression of the enzymes of DA synthesis in non-dopaminergic neurons is one of the adaptive reactions serving to compensate the functional insufficiency of DA-ergic neurons. For instance, hyperprolactinemia and the deficiency of DA, prolactin-inhibiting hormone, which is developed under degeneration of DA-ergic neurons of the arcuate nucleus, are compensated with time due to the increase of the number of monoenzymatic neurons and cooperative synthesis of DA in the nucleus. It is supposed that the same compensatory cooperative synthesis of DA is turned on under the degeneration of DA-ergic neurons of the nigrostriatal system that is manifested by the appearance of non-dopaminergic neurons expressing enzymes of DA synthesis in the deafferentated striatum. The expression of the enzymes of DA synthesis in non-dopaminergic neurons is under the control by intercellular signals, catecholamines, neurotrophic (growth) factors and, perhaps, hormones. Thus, non-dopaminergic monoenzymatic neurons expressing enzymes of DA synthesis produce this neurotransmitter in cooperation that is a compensatory reaction under functional insufficiency of DA-ergic neurons, in neurodegenerative diseases, hyperprolactinemia and Parkinson's disease, in particular.     

Blockade of NK3R signaling in the PVN decreases vasopressin and oxytocin release and c-Fos expression in the magnocellular neurons in response to hypotension

Tachykinin neurokinin 3 receptor (NK3R) signaling has a broad role in vasopressin (VP) and oxytocin (OT) release. Hydralazine (HDZ)-induced hypotension activates NK3R expressed by magnocellular neurons, increases plasma VP and OT levels, and induces c-Fos expression in VP and OT neurons. Intraventricular pretreatment with the specific NK3R antagonist, SB-222200, eliminates the HDZ-stimulated VP and OT release. NK3R are distributed in the central pathways conveying hypotension information to the magnocellular neurons, and the NK3R antagonist could act anywhere in the pathways. Alternatively, the antagonist could act at the NK3R expressed by the magnocellular neurons. To determine whether blockade of NK3R on magnocellular neurons impairs VP and OT release to HDZ, rats were pretreated with a unilateral PVN injection of 0.15 M NaCl or SB-222200 prior to an intravenous injection of 0.15 M NaCl or HDZ. Blood samples were taken, and brains were processed for VP/c-Fos and OT/c-Fos immunohistochemistry. Intravenous injection of 0.15 M NaCl did not alter plasma hormone levels, and little c-Fos immunoreactivity was present in the PVN. Conversely, intravenous injection of HDZ increased plasma VP and OT levels and c-Fos expression in VP and OT magnocellular neurons. Intra-PVN injection of SB-222200 prior to an intravenous injection of HDZ significantly decreased c-Fos expression in both VP and OT neurons by approximately 70% and attenuated plasma VP and OT levels by 33% and 35%, respectively. Therefore, NK3R signaling in magnocellular neurons has a critical role for the release of VP and OT in response to hypotension.     

The effect of chronic chlorpromazine administration on monoamine levels in various regions of rat brain

The neuroleptic drug, chlorpromazine (CPZ) has been shown to exert its antipsychotic effect by blocking post synaptic dopamine receptors. However, its effect on steady state levels of monoamines is still in discrepancy. In the present study, CPZ (4 mg/kg body weight) was administered intraperitoneally to adult Wistar rats chronically for 75 days and the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) were assayed in various brain regions by high performance liquid chromatography (HPLC). After the experimental period body and brain weights were not statistically different from controls. NE and 5-HT levels were increased only in hippocampus by 15% (p<0.01) and 16% (p<0.01) respectively. DA levels were consistently increased in cortex by 39% (p<0.001), striatum-accumbens by 18% (p<0.01), hippocampus by 27% (p<0.01), hypothalamus by 34% (p<0.001), cerebellum by 36% (p<0.001) and brainstem by 40% (p<0.001) in CPZ treated rats compared to controls. The results suggest that chronic CPZ administration increases DA levels in almost all regions of brain and reflect the ability of CPZ to preferentially interfere with synaptic transmission mediated by DA in brain. It also suggests that this increase in DA might be responsible for certain side effects seen in patients after chronic CPZ treatment.     

MIF-1 and its peptidomimetic analogs attenuate haloperidol-induced vacuous chewing movements and modulate apomorphine-induced rotational behavior in 6-hydroxydopamine-lesioned rats

Two melanocyte-stimulating hormone release inhibiting factor-1 (MIF-1) also known as L-prolyl-L-leucyl-glycinamide (PLG) peptidomimetic analogs, 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]-amino]-3-(butyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (A) and 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]amino]-3-(benzyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (B), were evaluated for their ability to modulate dopaminergic activity by measuring apomorphine-induced rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats, and haloperidol (HP)-induced vacuous chewing movements (VCMs) in rats; animal models of Parkinson's disease (PD) and human tardive dyskinesia (TD), respectively. In the 6-OHDA model, both analogs were found to potentiate the contralateral rotational behavior induced by apomorphine dose-dependently and with approximately the same potency. Furthermore, each analog was able to significantly attenuate HP-induced VCMs with almost equal efficacy. The potency and efficacy of these analogs were significantly greater than their parent compound, PLG. These results suggest that both analogs can modulate dopaminergic activity in vivo, likely by the same mechanisms recruited by PLG previously reported.     

Vasopressin and oxytocin release evoked by NaCl loads are selectively blunted by area postrema lesions

The present study investigated the effect of area postrema lesions (APX) on stimulated neurohypophysial secretion of vasopressin (VP) and oxytocin (OT) in conscious rats. Blunted increases in plasma levels of both pituitary hormones were observed when rats with APX were infused intravenously with 1 M NaCl solution (2 ml/h for 6 h). In contrast, plasma VP and OT increased normally in rats with APX when equivalent increases in plasma osmolality (but not plasma Na(+)) resulted from intravenous infusion of an equiosmotic solution of 1 M mannitol and 0.5 M NaCl. Furthermore, APX did not affect increases in plasma VP and OT stimulated by plasma volume deficits, nor did APX disrupt OT secretion stimulated by intravenous injection of cholecystokinin. These findings suggest that the area postrema plays an important role in mediating secretion of VP and OT in response to an NaCl load, but not in response to an equiosmotic load that does not cause substantial hypernatremia, and not in response to other stimuli of neurohypophysial hormone secretion. Together with previous reports, these results suggest that APX impairs Na(+) regulation in rats.     

Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro.

Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.     

Water ingestion provides an early signal inhibiting osmotically stimulated vasopressin secretion in rats

Dehydrated dogs are known to inhibit secretion of vasopressin (VP) within minutes after drinking water, before plasma osmolality (P(osmol)) diminishes. The present studies determined whether water ingestion causes a similar rapid inhibition of neurohypophyseal hormone secretion in rats. Adult rats were infused with 1 M NaCl (2 ml/h iv) for 240 min to stimulate VP and oxytocin (OT) secretion. After 220 min of infusion, rats were given water to drink for 5 min, and blood samples were taken 5 and 15 min later for RIA. Plasma VP (pVP) was much lower when rats ingested water than when they drank nothing even though P(osmol) was not significantly altered. Plasma OT (pOT) was affected similarly. In contrast, no effects on pVP or pOT occurred when rats drank isotonic NaCl solution for 5 min in amounts comparable to the water intakes (approximately 5.5 ml). These results suggest that neurohypophyseal secretion of VP and OT in rats is inhibited rapidly by water drinking, and that this inhibition is mediated by a visceral signal of osmotic dilution rather than by the act of drinking per se.     

Compensatory reaction during degeneration of arcuate nucleus dopaminergic neurons in rats

The study has been carried out to verify the authors' hypothesis that degeneration of dopaminergic (DA-ergic) neurons of the hypothalamic tuberoinfundibular system and concomitant development of hyperprolactinemia are accompanied by involvement of compensatory synthesis of dopamine (DA) by non-dopaminergic neurons expressing single complementary enzymes of synthesis of this neurotransmitter. Degeneration of DA-ergic neurons was produced by a stereotaxic injection into the brain lateral ventricles of 6-hydroxydopamine (6-OHDA) - a specific neurotoxin of DA-ergic neurons. 14 and 45 days after the toxin administration there were determined concentration of prolactine in peripheral blood by methods of immunoenzyme and radioimmunological analyses as well as the DA amount in the arcuate nucleus by the method of highly efficient liquid chromatography with electrochemical detection. In a part of the animals, slices were prepared from the mediobasal hypothalamus (arcuate nucleus and medial eminence) and perfused with Krebs-Ringer medium; then the DA concentration was determined in the slices and in the incubation medium. 14 days after the neurotoxin administration there were revealed an increase of blood prolactine concentration and a decrease of DA concentration in the arcuate nucleus in vivo as well a decrease of the total DA amount in the slices and incubation medium in experiments in vitro. 45 days after the neurotoxin administration, all the above parameters returned to the normal level. This, the obtained data indicate that the hyperlactinemia and DA deficit appearing during degeneration of the arcuate nucleus DA-ergic neurons seem to be compensated due to an enhancement of DA synthesis by non-dopaminergic monoenzyme neurons of arctuate nucleus.     

Role of non-NMDA receptors in vasopressin and oxytocin release from rat hypothalamo-neurohypophysial explants

Glutamate is recognized as a prominent excitatory transmitter in the supraoptic nucleus (SON) and is involved in transmission of osmoregulatory information from the osmoreceptors to the vasopressin (VP) and oxytocin (OT) neurons. Explants of the hypothalamo-neurohypophysial system were utilized to characterize the roles of the non-N-methyl-D-aspartate (NMDA) glutamate receptor subtypes (non-NMDA-Rs), kainic acid receptors (KA-Rs), and aminopropionic acid receptors (AMPA-Rs) and to evaluate the interdependence of NMDA-Rs and non-NMDA-Rs in eliciting hormone release. Although both KA and AMPA increased hormone release, a specific agonist of the KA-Rs, SYM-2081, was not effective. This combined with the finding that cyclothiazide, an agent that inhibits the desensitization of AMPA-Rs, increased the VP response to both KA and AMPA indicates that the increase in hormone release induced by the non-NMDA agonists is mediated via AMPA-Rs, rather than KA-Rs. Inhibition of osmotically stimulated VP and OT release by a specific AMPA-R antagonist indicated that AMPA-Rs are essential for mediating osmotically stimulated hormone release. NMDA-stimulated VP but not OT release was prevented by blockade of non-NMDA-Rs, but AMPA-stimulated VP/OT release was not prevented by NMDA-R blockade.     

Compensatory reaction during degeneration of arcuate nucleus dopaminergic neurons in rats

The study has been carried out to verify the authors’ hypothesis that degeneration of dopaminergic (DA-ergic) neurons of the hypothalamic tuberoinfundibular system and concomitant development of hyperprolactinemia are accompanied by involvement of compensatory synthesis of dopamine (DA) by non-dopaminergic neurons expressing single complementary enzymes of synthesis of this neurotransmitter. Degeneration of DA-ergic neurons was produced by a stereotaxic injection into the brain lateral ventricles of 6-hydroxydopamine (6-HDA)—a specific neurotoxin of DA-ergic neurons. 14 and 45 days after the toxin administration there were determined concentration of prolactine in peripheral blood by methods of immunoenzyme and radioimmunological analyses as well as the DA amount in the arcuate nucleus by the method of highly efficient liquid chromatography with electrochemical detection. In a part of the animals, sections were prepared from the mediobasal hypothalamus (arcuate nucleus and medial eminence) and perfused with Krebs—Ringer medium; then the DA concentration was determined in the sections and in the incubation medium. 14 days after the neurotoxin administration there were revealed an increase of blood prolactine concentration and a decrease of DA concentration in the arcuate nucleus in vivo as well a decrease of the total DA amount in the sections and incubation medium in experiments in vitro. 45 days after the neurotoxin administration, all the above parameters returned to the normal level. Thus, the obtained data indicate that the hyperlactinemia and DA deficit appearing during degeneration of the arcuate nucleus DA-ergic neurons seem to be compensated due to an enhancement of DA synthesis by non-dopaminergic monoenzyme neurons of arcuate nucleus.     

A rat model of Parkinsonism shows depletion of dopamine in the retina

The retinal dopamine (DA) deficiency is an important feature of the pathogenesis in Parkinson's disease (PD) visual dysfunction. Systemic inhibition of complex I (rotenone) in rats has been proposed as a model of PD. In this study, we investigated whether systemic inhibition of complex I can induce impairment of DA-ergic cells in the retina, similar to the destruction of retinal cells found in PD patients. Rotenone (2.5mg/kg i.p., daily) was administered over 60 days. Neurochemically, rotenone treated rats showed a depletion of DA in the striatum and substantia nigra (SN). In addition, the number of retinal DA-ergic amacrine cells was significantly reduced in the rotenone treated animals. This study is the first one giving highlight towards a deeper understanding of systemic complex I inhibition (rotenone as an environmental toxin) and the connection between both, DA-ergic degeneration in the nigrostriatal pathway, and in the DA-ergic amacrine cells of the retina.     

Effect of intracerebral administration of NMDA and AMPA on dopamine and glutamate release in the ventral pallidum and on motor behavior

The present study investigates the modulation of the ventral tegmental area (VTA)-ventral pallidum (VP) dopaminergic system by glutamate agonists in rats. The glutamate receptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were infused via reversed microdialysis into the VTA, and dopamine (DA), glutamate, and aspartate levels in the VTA and ipsilateral VP were monitored together with motor behavior screened in an open field. NMDA (750 microM) infusion, as well as AMPA (50 microM) infusion, induced an increase of DA and glutamate levels in the VTA, followed by an increase of DA levels in the ipsilateral VP and by enhanced locomotor activity. The increase of DA in the VP was similar after administration of these two glutamate agonists, although motor activity was more pronounced and showed an earlier onset after NMDA infusion. Glutamate levels in the VP were not increased by the stimulation of DA release. It is concluded that DA is released from mesencephalic DA neurons projecting to the VP and that these neurons are controlled by glutamatergic systems, via NMDA and AMPA receptors. Thus, DA in the VP has to be considered as a substantial modulator. Dysregulation of the mesopallidal DA neurons, as well as their glutamatergic control, may play an additional or distinct role in disorders like schizophrenia and drug addiction.     

Effect of Precursors on the Synthesis of Catecholamines and on Neurotransmission in the Superior Cervical Ganglion of the Rat

Abstract: Male Sprague-Dawley rats (325–350 g) were anesthetized with urethane (1.5 g/kg i.p.) and treated with physiological saline, Aspartame (APM; 552 μmol/kg), or tyrosine (Tyr; 552 μmol/kg). Ganglionic transmission and the synthesis of dopamine (DA) and norepinephrine (NE) were measured in the superior cervical ganglion (SCG) following electrical stimulation of the cervical sympathetic trunk (CST). When the CST was stimulated with single pulses, neither APM nor Tyr affected the synthesis of NE or DA. However, in response to low- (5 Hz, 20 s) and high- (20 Hz, 20 s) frequency pulses, the metabolism of DA was increased (p > 0.05), but to the same extent after saline, APM, or Tyr. In rats stimulated with similar low- and high-frequency pulses, the synthesis of NE was increased significantly (p > 0.05) after Tyr, but not after APM or saline. In saline-treated controls, ganglionic transmission was not changed in response to single pulses, or low- or high-frequency stimulation. However, after treatment with APM, ganglionic transmission was depressed significantly (p > 0.01) in response to high-frequency stimulation (single: 0.46 ± 0.09 mV; low: 0.39 ± 0.07 mV; high: 0.27 ± 0.07 mV). After treatment with Tyr, ganglionic transmission was depressed significantly (p > 0.05) in response to both low- and high-frequency stimulation (single: 0.44 ± 0.04 mV; low: 0.22 ±0.12 mV; high: 0.26 ± 0.07 mV). In the nonstimulated SCG, l-3,4-dihydroxyphenylalanine (25 mg/kg) caused a rapid, significant (p > 0.01) increase in the synthesis and metabolism of DA, but not of NE. Treatment with nialamide (200 mg/kg i.p.) followed by electrical stimulation (15 Hz, 15 min) of the CST caused a significant (p > 0.05) increase of both NE and DA in the stimulated SCG. It is concluded that there are both similarities and differences in the regulation of the synthesis of NE and in the modulation of ganglionic transmission after the administration of the precursors APM and Tyr. The results indicate that caution is needed in comparing the neurochemical and neurophysiological effects of different catecholamine precursors.