Cardiovascular effects of nitric oxide and adenosine in the nucleus tractus solitarii of rats

It has been shown that nitric oxide (NO) is synthesized in the central nervous system as well as in vascular endothelial cells. We recently reported that NO was involved in central cardiovascular regulation, modulated the baroreflex, and was involved in a reciprocal release with excitatory amino acids in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine increased the release of glutamate in the NTS. The purpose of the present study was to investigate the possible interaction of NO and adenosine in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Unilateral microinjection of L-arginine (3.3 nmol/60 nL) into the NTS produced decreases in blood pressure and heart rate. Microinjection of adenosine (2.3 nmol/60 nL) also produced depressive and bradycardic effects. These cardiovascular effects were attenuated by prior administration of the specific adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, prior administration of NO synthase inhibitor NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester significantly attenuated the depressive and bradycardic effects of adenosine. These results demonstrate a reciprocal attenuation of adenosine receptor antagonist and NO synthase inhibitor on L-arginine and adenosine responses, respectively, in the NTS and implicate an interaction between NO and adenosine in central cardiovascular regulation.     

Direct evidence for nitric oxide synthase in vagal afferents to the nucleus tractus solitarii

The anatomical relationship between vagal afferents and brain nitric oxide synthase containing terminals in the nucleus tractus solitarii was studied by means of anterograde tracing combined with immunocytochemistry and immuno-electron microscopy. Biotinylated dextran amine was injected into the nodose ganglion with a glass micropipette. Four to eight days following the injection, regions of the nucleus tractus solitarii containing biotinylated dextran amine-labelled vagal afferents and those containing nitric oxide synthase-immunopositive terminals were congruent. Many neurons exhibiting nitric oxide synthase immunoreactivity were found within the biotinylated dextran amine-containing terminal field. However dense labeling of terminals with biotinylated dextran amine precluded determination if the terminals were nitric oxide synthase-immunoreactive. Therefore, we combined degeneration of vagal afferents after removal of one nodose ganglion with nitric oxide synthase immuno-electron microscopy. Axon terminals that possessed characteristic vesicle clusters and were partially or completely engulfed by glial processes were identified as degenerating vagal afferents. Degenerating axon terminals comprised 38% of the total axon terminals in the nucleus tractus solitarii in a sample of sections; and of the degenerating axon terminals, 67% were nitric oxide synthase-immunoreactive. Nitric oxide synthase immunoreactivity was present in 41% of the non-degenerating axon terminals. Prominent staining of dendrites for nitric oxide synthase immunoreactivity indicated that much of the nitric oxide synthase in the nucleus tractus solitarii is not derived from peripheral afferents. Of the total number of dendritic profiles sampled, half were nitric oxide synthase-immunoreactive. Our data support the hypothesis that nitric oxide or nitric oxide donors may be present in primary vagal afferents that terminate in the nucleus tractus solitarii. While this study confirms that vagal afferents contain brain nitric oxide synthase, it demonstrates for the first time that the majority of nitric oxide synthase immunoreactivity in the nucleus tractus solitarii is found in intrinsic structures in the nucleus. In addition, our data show that second or higher order neurons in the nucleus tractus solitarii may be nitroxidergic and receive both nitroxidergic and non-nitroxidergic vagal input.     

Prostaglandin E2 facilitates excitatory synaptic transmission in the nucleus tractus solitarii of rats

Intrinsic membrane properties and synaptic responses of neocortical neurons located lateral to photochemically induced ischemic lesions were investigated using neocortical slice preparation. In comparison to neurons from control slices, these neurons had a significantly less negative resting membrane potential without any significant change in input resistance. In addition, gamma-aminobutyric acid (GABA) mediated synaptic inhibition was found to be less efficient; the conductances of both the early and late inhibitory postsynaptic potentials (IPSPs) were significantly smaller, and the reversal potential of the early IPSP was shifted to a more positive value. In some of the neurons, 'epileptiform' postsynaptic potentials could be elicited, which were abolished after wash-in of the N-methyl-D-aspartic acid (NMDA)-receptor antagonist D-2-amino-5-phosphonovaleric acid (AP-5). The results provide a possible explanation for the hyperexcitability found in the vicinity of cortical infarcts.     

Inhibition of glycine currents by dextromethorphan in neurones dissociated from the guinea-pig nucleus tractus solitarii

1. The effect of dextromethorphan (DM) on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique. The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (IGABA) was also examined. 2. DM inhibited 30 microM glycine-induced current (IGly), without affecting the current caused by 30 microM GABA. The action of DM was concentration-dependent, with a maximum effect at 100 microM, and reversible. The half-maximum inhibitory concentration (IC50) of DM was 3.3 microM, about 85 times higher than that of strychnine. 3. DM 3 microM shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 microM shifted the curve even more to the right, although it was not a parallel shift. Strychnine at a concentration of 0.1 microM shifted the curve for glycine in a nearly parallel fashion. 4. The effect of 10 microM DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 microM, inhibited IGly equally at -50 mV and +50 mV. The effect of 3 microM DM on IGly showed no use-dependence. Blockade by strychnine 0.1 microM showed no voltage- or use-dependence. 5. The results indicate that DM inhibits IGly in single neurones of NTS, and further suggest that DM at a low concentration may act on the glycine receptor-ionophore complex, but not on the Cl channel of the complex. However, a relatively high concentration of DM may at least partly affect the Cl- channel of the complex.     

Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1 beta

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.     

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.     

Environmental events that modify the catecholamine fluorescence of the A2 cell bodies in nucleus tractus solitarii.

Found that the fluorescence intensity of the catecholamine cell bodies of the A2 group--as determined by microfluorimetry--increased significantly due to exposure of male rats of the Sprague-Dawley-Ivanovas strain to the following environmental events: placement from the colony cage into a cold (4°C) room for a period of 10 min, isolation from the colony for 6-7 days, and satiation of grouped Ss by allowing access to sweetened milk for 15 min. The following events failed to affect the intensity of the cells of A2: reduction of the group colony size from 8 to 3 rats per colony for 6-7 days and presentation of water instead of milk after the rats had experienced 6-7 days of milk satiation. Results indicate that aversive as well as rewarding environmental events activate the catecholamine cells of A2. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Elevated Fos expression in the nucleus tractus solitarii is associated with reduced baroreflex response in spontaneously hypertensive rats

We delineated the functional role of Fos protein at the nucleus tractus solitarii in the manifestation of reduced baroreceptor reflex control of heart rate during hypertension, using spontaneously hypertensive rats (SHR), stroke-prone SHR, Wistar-Kyoto rats, or Sprague-Dawley rats. Microinjection into the bilateral nucleus tractus solitarii of an antisense oligonucleotide that targets against the initiation codon of c-fos mRNA significantly potentiated the baroreceptor reflex in response to 30 minutes of sustained increase in blood pressure. Of particular note was the restoration of both the impaired sensitivity and capacity of baroreceptor reflex in SHR and stroke-prone SHR to levels comparable to those in normotensive rats. Likewise, the number of Fos-immunoreactive nuclei evoked by the sustained increase in blood pressure in the caudal nucleus tractus solitarii of SHR and stroke-prone SHR was reduced, after this antisense c-fos treatment, to the basal level exhibited by the normotensive animals. Control treatment with the corresponding sense oligonucleotide, an antisense oligonucleotide that targets against a different portion of the coding sequence of the c-fos mRNA or artificial cerebrospinal fluid, on the other hand, elicited no discernible effect on either the baroreceptor reflex response or the induced expression of Fos protein in the nucleus tractus solitarii by baroreceptor activation. We also found that the basal level of Fos expression in the caudal nucleus tractus solitarii was significantly elevated in the SHR and stroke-prone SHR. Together, these novel findings suggest that an elevated expression of basal Fos protein in the NTS during hypertension may be associated with the dysfunction in baroreceptor reflex control of heart rate.     

Localization of tyrosine hydroxylase in neuronal targets and efferents of the area postrema in the nucleus tractus solitarii of the rat

Catecholamines in the nucleus tractus solitarii (NTS) have been implicated in autonomic responses to circulating hormones that act on neurons in the area postrema, the most caudal circumventricular organ in brain. We combined immunoperoxidase labeling of the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHAL) with immunogold-silver labeling of tyrosine hydroxylase to determine whether this enzymatic marker for catecholamines was present in efferents from the area postrema or their targets in the rat NTS. At survival periods of 10-12 days after PHAL injections into the area postrema, light microscopy revealed numerous varicose processes containing peroxidase reaction product for PHAL in the dorsomedial, medial, and commissural NTS. Some of these labeled processes were located near neuronal perikarya and processes containing immunogold-silver intensified reaction product for tyrosine hydroxylase. Electron microscopy of the commissural and dorsomedial NTS established that the majority of the labeling for PHAL was in axon terminals, whereas immunogold labeling for tyrosine hydroxylase was mainly in soma and dendrites. Only 3 out of 579 PHAL-labeled terminals also contained detectable tyrosine hydroxylase immunoreactivity. Fifty-eight percent (335/579) of the PHAL-labeled terminals formed synapses with recognized symmetric junctions, whereas the remainder lacked synaptic specializations within the examined series of serial sections. Of those PHAL terminals forming recognized symmetric junctions, 22% were on tyrosine hydroxylase-immunoreactive dendrites, 74% on unlabeled dendrites and 4% on unlabeled axon terminals. From a total of 1,250 observed contacts on tyrosine hydroxylase labeled dendrites, 88 (7%) contained PHAL, 9 (< 1%) contained TH, and 1,180 (93%) lacked detectable immunoreactivity and formed primarily symmetric synapses. We conclude that a few catecholamine, but mainly noncatecholamine efferents from the area postrema provide a monosynaptic, and most likely inhibitory input to target neurons both with and without tyrosine hydroxylase immunoreactivity in the dorsomedial and commissural NTS. Synapses between the efferent terminals from the area postrema and tyrosine hydroxylase labeled and unlabeled dendrites as well as unlabeled axons in these specific subnuclei of the NTS suggest multiple sites for modulation of gastric and cardiovascular reflexes in response to circulating peptides.     

Whole-cell analysis of ionic currents underlying the firing pattern of neurons in the gustatory zone of the nucleus tractus solitarii

1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mediation by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors in the expression of Fos protein at the nucleus tractus solitarii in response to baroreceptor activation in the rat

The extent of variation in reptile field metabolism, and its causal bases, are poorly understood. We studied the energetics of the insectivorous lizard Callisaurus draconoides at a site in the California Desert (Desert Center) and at a site at the southern tip of the Baja Peninsula (Cabo San Lucas; hereafter, Cabo). Reproducing Callisaurus were smaller at Cabo than at Desert Center. The allometry of metabolism with body mass can account for most differences in whole-animal metabolism. There was no significant effect of sex or source population on mass-adjusted metabolic rate in the laboratory (resting metabolism, measured by closed-system respirometry) or in the field (field metabolism, measured with doubly labeled water). The mass-adjusted resting metabolism and field metabolism of gravid females and the field metabolism of juvenile lizards were not significantly different from those of nonreproductive adults. Temperature had a significant effect on resting metabolism (Q10 = 2.7); fed lizards had resting metabolism that was 22% higher than that of fasted lizards; field metabolism was positively correlated with growth rate in juveniles; and field metabolism of adults increased from spring to late summer at Desert Center by 25%, probably because of longer activity period length and slightly higher activity period body temperature. We calculated from water influx and field metabolism that juveniles allocated 18% of their metabolizable energy intake to growth and that most energy deposited into eggs was transferred from energy stores rather than ingested in the weeks prior to laying.     

Autoradiographic determination of local cerebral blood flow and local cerebral glucose utilization during chemical stimulation of the nucleus tractus solitarii of anesthetized rats

This study was conducted to determine whether the decrease in cerebral blood flow (CBF) observed during chemical stimulation of the nucleus tractus solitarius (NTS) can be explained by a decrease in cerebral metabolism. In anesthetized (urethane and chloralose), paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of L-glutamate. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were quantified in 43 brain structures by quantitative autoradiographic techniques using [14C]iodoantipyrine and 2-[14C]deoxyglucose, respectively. During chemical stimulation of the NTS (n = 6), LCBF decreased significantly in 32 of the 43 structures investigated when compared to either a control group with artificial cerebrospinal fluid injection (n = 6), or a controlled hemorrhage group (n = 5). In the controlled hemorrhage group, blood pressure was decreased to a degree comparable to that induced by microinjection of L-glutamate into the NTS. Mean blood flow of all structures investigated was significantly (P < 0.01) lower in the stimulation group than that in the control group and in the hemorrhage group. No significant differences in LCGU were observed between the three investigated groups in all structures examined except for an increase in LCGU in the chemically stimulated NTS site. It is concluded that the decrease in LCBF measured in most brain structures during chemical stimulation of the NTS is not caused by a decrease in LCGU in these structures and may therefore be explained by neurogenic influences on brain vessels.     

Discharge pattern of neurons in the nucleus tractus solitarii (NTS): its cardiac rhythm is modulated by firing rate of the neurons

In the nucleus tractus solitarii (NTS) neurons discharge in relation to cardiac rhythm. This cardiac rhythm exhibits various patterns designated as CRDPs (cardiac rhythmic discharge patterns). The CRDPs are estimated by post-event-time histograms (PETH) triggered by the R-waves of the ECG. Modulations of CRDPs appear as changes in the number and height of peaks in the PETHs. The amount of basic activity, which is not related to the cardiac cycle, alters CRDP. PETHs constructed during various phases of respiration reveal modulations of CRDPs within the respiratory cycle. As our previous work indicated, the NTS neurons exhibit typical reticular rhythms. In this paper we also found that the basic activity of NTS neurons was often changed by other influences for which no comparable patterns could be observed in other simultaneously acquired signals. When we constructed PETHs according to the activity level of the NTS neurons, i.e., firing level per cardiac cycle, modulations of CRDPs which were even stronger than respiratory or reticular rhythmical modulations became clear. The modulations of CRDPs caused by different origins were found to be present in the same neuron interlaced in time. The possible role played by these modulations of CRDPs in the coordination of different functional systems in the organism is discussed.     

Collateral projections of gamma-aminobutyric acid positive neurons from the lateral superior nucleus to the cochlea and cochlear nucleus in guinea pigs

Collateral projections of gamma-aminobutyric acid (GABA) neurons from the lateral superior olivary nucleus (LSO) to the cochlea and cochlear nuclei in the guinea pigs were studied by injection of two retrograde fluorescent neuronal tracers. For experiments, fast blue (FB) was injected into the scala tympani of one cochlea and diamidine yellow (DY) was injected into cochlear nuclei of the same side. The results showed that the FB-labelled cells and DY-labelled cells constituted approximately 80.8% and 12.4%, respectively; FB and DY double-labelled cells constituted about 6%; FB and DY labelled cells with GABA constituted about 0.7% in the ipsilateral LSO. In the contralateral LSO, the FB and DY labelled cells were less than those of ipsilateral LSO and no FB-DY double-labelled cells could be found. Our results suggest that there are collateral projections of GABA neurons from ipsilateral LSO to the organ of Corti and cochlear nuclei in the guinea pig, even though the numbers are few. The results also show that the efferent projections to the cochlea and cochlear nuclei generally come from two different auditory neuronal nuclei.     

Dorsal column inhibition of nociceptive thalamic cells mediated by gamma-aminobutyric acid mechanisms in the cat

Cells derived from mice homozygous for the severe combined immune deficiency (scid) mutation exhibit hypersensitivity to ionizing radiation, and defects in DNA double-strand break repair and V(D)J recombination. Using the technique of microcell-mediated chromosome transfer, we have introduced a number of dominantly marked human chromosomes into scid cells to localize the human homolog of the murine scid gene. Analysis of human-scid hybrid clones revealed that the presence of human chromosome 8 partially restored accurate V(D)J recombination and radioresistance to scid cells. Subsequent loss of the human chromosome 8 from human-scid hybrid clones rendered these cells sensitive to gamma-radiation and impaired their ability to catalyse V(D)J recombination. Introduction of chromosomes 2, 14, 16 and 19 that encode other repair genes did not result in the correction of these two scid defects. These observations demonstrate that the human homolog of the mouse scid gene resides on human chromosome 8.     

Participation of AT1 and AT2 receptor subtypes in the tonic inhibitory modulation of baroreceptor reflex response by endogenous angiotensins at the nucleus tractus solitarii in the rat

Although myelin basic protein (MBP)-recognizing T cells are not readily obtained after immunization of BALB/c mice with MBP (reflecting the BALB/c resistance to actively induced experimental autoimmune encephalomyelitis (EAE)), they can be expanded and cloned after several rounds of in vitro culture. The majority of BALB/c-derived clones recognize an epitope defined by MBP peptide 59-76. When transferred to naive BALB/c recipients, these clones cause classical EAE, with characteristic inflammation and demyelination of the central nervous system (CNS). We previously showed that two related clones recognizing a minor epitope, defined by MBP peptide 151-168, cause inflammation and demyelination preferentially of the peripheral nervous system (PNS). Because MBP has alternatively spliced isoforms, residues 151-168 are not present contiguously in all MBP isoforms. In order to determine whether induction of PNS disease is idiosyncratic to these sister clones, or related to their properties of epitope recognition, an independent T-cell line with similar recognition properties was studied. Clone 116F, derived from a BALB/c shiverer mouse, expresses a different T-cell receptor (TCR), with distinct TCR contact residues, but like the previously described T cells, this clone requires residues from both exons 6 and 7 for optimal stimulation. When adoptively transferred to BALB/c recipients, this clone preferentially induces disease of the PNS. A control BALB/c shiverer-derived MBP 59-76-recognizing clone, in contrast, induces CNS disease. These data strongly suggest that the site of disease initiation may correlate with epitope recognition, particularly when alternative isoforms are involved.     

A topographically organized gamma-aminobutyric acid projection from the ventral pallidum to the nucleus accumbens in the rat

Anatomical and electrophysiological studies have indicated that a reciprocal projection from the ventral pallidum back to the nucleus accumbens exists and has functional relevance. In this study, the topographical projection from the ventral pallidum to the nucleus accumbens was examined by using retrograde tracing with fluoro-gold iontophoresed in subcompartments of the nucleus accumbens in rats combined with either in situ hybridization for glutamic acid decarboxylase and preproenkephalin mRNA or substance P immunoreactivity. Deposits made into the medial nucleus accumbens preferentially labeled neurons in the medial ventral pallidum, while deposits into the dorsolateral nucleus accumbens, at or lateral to the anterior commissure, labeled primarily cells in the dorsal and lateral ventral pallidum. A mediolateral to rostrocaudal topography was also observed, with the medial deposits preferentially labeling cells in rostral ventral pallidum and the lateral deposits resulting in retrogradely labeled cells in the ventral pallidum below the crossing of the posterior anterior commissure (subcommissural) as well as below the globus pallidus (sublenticular). The majority of cells retrogradely labeled with fluoro-gold were double-labeled for glutamic acid decarboxylase mRNA. In contrast, very few retrogradely labeled neurons in the ventral pallidum were double labeled for mRNA for preproenkephalin. These data demonstrate a topographically organized projection from the ventral pallidum to the nucleus accumbens that is primarily gamma-aminobutyric acid (GABA)-ergic and reciprocal to the GABAergic projection from the nucleus accumbens to the ventral pallidum.     

The non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 blocks the [Leu31,Pro34]neuropeptide Y-induced modulation of alpha 2-adrenoceptors in the nucleus tractus solitarii of the rat

The potential blockade of the neuropeptide Y (NPY) Y1 receptor agonist [Leu31,Pro34]NPY-induced modulation of the characteristics of alpha 2-adrenoceptor agonist [3H]p-aminoclonidine binding sites by a selective non-peptide NPY Y1 receptor antagonist BIBP3226, was studied in the nucleus tractus solitarii of the rat by means of quantitative receptor autoradiography. [Leu31,Pro34]NPY at a concentration of 10 nM significantly increased the Kd value of [3H]p-aminoclonidine binding sites in the nucleus tractus solitarii without influencing the Bmax, suggesting the existence of an antagonistic modulation by NPY Y1 receptors of alpha 2-adrenoceptors in the nucleus tractus solitarii. BIBP3226 at 100 nM fully blocked the [Leu31,Pro34]NPY-induced increase in Kd of the [3H]p-aminoclonidine binding sites. The present results therefore provide evidence, by use of a NPY Y1 receptor antagonist, for the existence of a NPY Y1/alpha 2 receptor interaction in the nucleus tractus solitarii.