Localization of GABAB receptors in midbrain monoamine containing neurons in the rat

The localization of γ-aminobutyric acid (GABA)_B receptors in the midbrain of the rat was examined in multiple labeling studies using antibodies directed against the GABA_B receptor and either tryptophan hydroxylase or tyrosine hydroxylase. Almost all of the serotonergic and dopaminergic cell bodies in the midbrain displayed GABA_B receptor-like immunoreacrtivity. Conversely, most neurons in the raphe nuclei and ventral tegmentum which exhibited intense immunoreactivity for GABA_B receptors were also immunopositive for serotonergic or dopaminergic markers. These results demonstrate directly that GABA_B receptors are present in monoaminergic neurons in certain regions of the midbrain.     

Cholinergic neurons of the feline pontomesencephalon. II. Ascending anatomical projections

Immunoreactivity for choline acetyltransferase (ChAT) was analyzed in unoperated cats and in cats in which stereotaxic lesions were made in the pedunculopontine and laterodorsal tegmental nuclei. The fine reaction product revealed moderate to dense ChAT-immunoreactive fiber plexuses throughout the telencephalon, diencephalon, and midbrain. A pontomesencephalic origin of cholinergic innervation to virtually every nucleus of the diencephalon, as well as to various midbrain and basal telencephalic sites was indicated in the cats with lesions, in which the optical density of ChAT-immunoreactivity was significantly decreased as compared to controls. Pontomesencephalic lesions produced no changes, however, in the density of ChAT staining in the cerebral cortex, basolateral amygdala, or caudate nucleus. In addition to ChAT-positive terminal fiber arborizations which were widely distributed, cholinergic fibers-of-passage were traced in the unoperated and operated feline brains. The general course of ChAT fibers cut in cross-section was followed in successive transverse levels, and although pathways originating from the pedunculopontine nucleus demonstrated orientations in every direction, many demonstrated a rostral course. A particularly dense aggregate of ascending ChAT-positive fibers was localized in the dorsolateral sector of the pedunculopontine area which could be followed at more rostral levels into the central tegmental fields and the compact part of the substantia nigra. From the central tegmental fields, numerous ChAT-immunopositive fibers cut in cross-section continued to course rostrally in the intralaminar, reticular and lateroposterior nuclei of the thalamus, and a distinct bundle of ChAT fibers coursing dorsolaterally was observed medial to the optic tract ascending to the lateral geniculate. ChAT fibers with dorsolateral orientations were additionally observed in the zona incerta, ventral anterior thalamus, and ansa lenticularis on route to the reticular thalamus, the globus pallidus, and the substantia innominata. Pathways consisting of fibers traced from ChAT-containing cells in the laterodorsal tegmental nucleus could be traced to medial structures such as the periaqueductal gray, ventral tegmental area and dorsal raphe. Medially placed ChAT fibers were additionally followed through the ventral tegmental area, the midline thalamus, and the hypothalamus, up to the medial and lateral septal nuclei. The trajectories of the ascending cholinergic pathways from the pontomesencephalon are discussed in relation to locally generated electrophysiological responses in the cat.     

Electrophysiological and pharmacological characterization of identified nigrostriatal and mesoaccumbens dopamine neurons in the rat

Extracellular single-unit recording techniques were used to compare the basal activity and pharmacological responsiveness of identified nigrostriatal and mesoaccumbens dopamine (DA)-containing neurons. The projection area of each DA cell was determined by antidromic activation techniques. The forebrain stimulation used for the cell identification procedure did not alter the pharmacological responsiveness of DA neurons; the inhibitory effect of apomorphine (and d-amphetamine) was identical when stimulation was applied either prior to or following drug administration. Analysis of the spike discharge pattern revealed that a higher proportion of mesoaccumbens DA cells exhibited burst-firing activity. Although the firing pattern of the two populations of burst-firing DA cells was similar in many regards, mesoaccumbens DA cells exhibited a longer postburst inhibition than did nigrostriatal DA cells. Each of the DA agonists, apomorphine, pergolide, B-HT 920, and d-amphetamine, inhibited nigrostriatal and mesoaccumbens DA neuronal activity in a similar fashion. However, there was a marked population difference in the recovery of cell firing in the 10 minutes following apomorphine-induced inhibition; the recovery of mesoaccumbens spike discharges was considerably slower. Although this population difference was apparent to some extent following administration of pergolide or B-HT 920 (but not d-amphetamine), it was considerably less marked. The present findings are discussed with respect to the known regulatory control of midbrain DA neurons.     

D1 receptor activation enhances sciatic nerve stimulation-induced inhibition of nigrostriatal dopamine neurons

Nigrostriatal dopamine (NSDA) neurons have been hypothesized to play an important regulatory role in neostriatal sensorimotor integration. In order to provide further information on the nature of sensory modulation of NSDA cells, we have examined the pharmacology of the responsiveness of these neurons to peripheral nerve stimulation. The selective D1 dopamine receptor agonist SKF 38393 enhanced the normal inhibition of NSDA neurons produced by electrical stimulation of the sciatic nerve. The SKF 38393-induced enhancement, but not the basal stimulation-induced inhibition itself, was blocked by prior hemitransection of the forebrain and was reversed by the selective D1 antagonist SCH 23390 but not by the selective D2 antagonist 1-sulpiride. SCH 23390 alone, however, exerted no effect on this inhibition. The selective D1 receptor agonist fenoldopam, which does not cross the blood-brain barrier, also failed to alter the response to sciatic nerve stimulation (i.v. administration). Thus, central D1 receptors (rostral to the midbrain) appear to be involved in a system which mediates phasic control over sensory modulation of NSDA neuronal activity.     

Firing of ‘possibly’ cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness

To clarify functional roles of mesopontine cholinergic neurons as a component of an activating system, single neuronal activity in the laterodorsal tegmental nucleus (LDT) of undrugged rats, whose head was fixed painlessly, was recorded along with cortical EEG and neck EMG. Activity of some dorsal raphe (DR) neurons was also recorded for comparison. Most of the animals had been sleep-deprived for 24 h. Observation was made only on neurons generating broad spikes, presumed from previous studies to be cholinergic or monoaminergic. The position of recorded neurons was marked by Pontamine sky blue ejected from the glass pipette microelectrode, and was identified on sections processed for NADPH diaphorase histochemistry which specifically stained cholinergic neurons. According to their firing rates during wakefulness (AW), slow-wave sleep (SWS) and paradoxical sleep (PS), 46 broad-spike neurons in the LDT were classified into 4 groups: (1) neurons most active during AW and silent during PS (some of these neurons might be serotonergic rather than cholinergic, as all the 9 neurons in the DR); (2) neurons most active during PS and silent during AW; (3) neurons equally more active during AW and PS than SWS; and (4) others mainly characterized by transiently facilitated activity at awakening and/or onset of PS. Neurons of groups 2 and 3 were the major constituents of the LDT. In most neurons change in firing preceded EEG change, except at awakening from PS. These results suggest that: (1) the LDT is composed of cholinergic neurons with heterogenous characteristics in relation to sleep/wakefulness; and (2) some tegmental cholinergic neurons play a pivotal role in induction and maintenance of PS.     

Effects of chronic alcohol consumption and withdrawal on the cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei of the rat: An unbiased stereological study

The brain cholinergic system comprises two main recognized subdivisions, the basal forebrain and the brainstem cholinergic systems. The effects of chronic alcohol consumption on the basal forebrain cholinergic nuclei have been investigated extensively, but there is only one study that has examined those effects on the brainstem cholinergic nuclei. The last one comprises the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei, which are known to give origin to the main cholinergic projection to the ventral tegmental area, a key brain region of the neural circuit, the mesocorticolimbic system, that mediates several behavioral and physiological processes, including reward. In the present study, we have examined, using stereological methods, the effects of chronic alcohol consumption (6 months) and subsequent withdrawal (2 months) on the total number and size of PPT and LDT choline acetyltransferase (ChAT)-immunoreactive neurons. The total number of PPT and LDT ChAT-immunoreactive neurons was unchanged in ethanol-treated and withdrawn rats. However, ChAT-immunoreactive neurons were significantly hypertrophied in ethanol-treated rats, an alteration that did not revert 2 months after ethanol withdrawal. These results show that prolonged exposure to ethanol leads to long-lasting, and potentially irreversible, cytoarchitectonic and neurochemical alterations in the brainstem cholinergic nuclei. These alterations suggest that the alcohol-induced changes in the brainstem cholinergic nuclei might play a role in the mechanisms underlying the development of addictive behavior to alcohol.     

Inhibitory and indirect excitatory effects of dopamine on sympathetic preganglionic neurones in the neonatal rat spinal cord in vitro

Regions of the thoraco-lumbar spinal cord containing sympathetic preganglionic neurones are rich in dopamine terminals. To determine the influence of this innervation intracellular recordings were made from antidromically identified sympathetic preganglionic neurones in (400 micrometers) transverse neonatal rat spinal cord slices. Dopamine applied by superfusion caused a slow monophasic hyperpolarisation in 46% of sympathetic preganglionic neurones, a slow monophasic depolarisation in 28% of sympathetic preganglionic neurones and a biphasic effect consisting of a slow depolarisation followed by a slow hyperpolarisation or vice-versa in 23% of sympathetic preganglionic neurones. Three percent of sympathetic preganglionic neurones did not respond to the application of dopamine. Low Ca2+/high Mg2+ Krebs solution or TTX did not change the resting membrane potential but abolished the slow depolarisation elicited by dopamine, indicating this was synaptic and did not prevent the dopamine induced hyperpolarisation. The dopamine induced slow hyperpolarisation was mimicked by the selective D1 agonists SKF 38393 or SKF 81297-C and blocked by superfusion with the D1 antagonist SCH 23390. It was not prevented by superfusion of the slices with alpha1 or alpha2 or beta-adrenoceptor antagonists, whereas the inhibitory or excitatory actions of adrenaline were prevented by alpha1 or alpha2 antagonists, respectively. The dopamine induced slow depolarisation occurring in a sub-population of sympathetic preganglionic neurones was mimicked by quinpirole, a D2 agonist, and blocked by haloperidol, a D2 antagonist. Haloperidol did not block the dopamine induced hyperpolarisations. Dopamine also induced fast synaptic activity which was mimicked by a D2 agonist and blocked by haloperidol. D1 agonists did not elicit fast synaptic activity.     

Glutamatergic afferent projections to the dorsal raphe nucleus of the rat

Based on WGA-apo-HRP-gold (WG) retrograde tracing, the present study revealed that different subdivisions of the dorsal raphe (DR) such as dorsomedial, ventromedial, lateral wing, and caudal regions receive unique, topographically organized afferent inputs, that are more restricted than previously reported. Phaseolus vulgaris leucoagglutinin anterograde tracing studies confirmed that the medial prefrontal cortex provides the major afferent input to each subdivision of the DR. Double-labeling studies combining WG tracing and glutamate immunostaining indicated that the medial prefrontal cortex, various hypothalamic nuclei including perifornical, lateral, and arcuate nuclei, and several medullary regions such as lateral and medial parabrachial nuclei, and laterodorsal tegmental nucleus provide the major glutamatergic input to each subregion of the DR. It should be noted that the degree of glutamatergic input from these afferent sites was specific for each DR subdivision. The present findings indicated that dorsomedial, ventromedial, lateral wing, and caudal subdivisions of the DR receive excitatory inputs from both cortical and subcortical sites which might be involved in regulation or modulation of a broad range of systems, including sensory and motor functions, arousal and sleep-wake cycle, biorhythmic, cognitive, and affective behaviors.     

Serotonergic regulation of inhibitory avoidance and one-way escape in the rat elevated T-maze

It has been proposed that distinct 5-HT pathways modulate different types of anxiety. Activation of the ascending dorsal raphe (DR)-5-HT pathway, innervating the amygdala and frontal cortex, would facilitate learned defensive behaviors. On the other hand, activation of the DR-periventricular 5-HT pathway, which innervates the dorsal periaqueductal gray matter (DPAG), would inhibit innate flight or fight reactions. Dysfunction of these pathways has been suggested to relate to generalized anxiety disorder (GAD) and panic disorder (PD) in humans, respectively. The elevated T-maze has been developed to separate conditioned (inhibitory avoidance) from unconditioned (escape) defensive responses in the same rat. Pharmacological validation of this model has shown that the GAD-effective serotonergic anxiolytic buspirone or the putative anxiolytic ritanserin selectively impaired inhibitory avoidance while leaving one-way escape unchanged. Chronic injection of the 5-HT/noradrenaline reuptake inhibitor imipramine impaired inhibitory avoidance and prolonged escape, an effect that may be related to the therapeutic action of this drug on both GAD and PD. Like imipramine, intra-DPAG injection of the 5-HT_1A agonist 8-OH-DPAT impaired both inhibitory avoidance and one-way escape. Intra-DPAG administration of the 5-HT_2A/2C agonist DOI prolonged escape, without affecting inhibitory avoidance. The reversible inactivation of the DRN by muscimol impaired inhibitory avoidance, while facilitating escape from the open arm. Taken together, these results suggest that 5-HT exerts differential control on inhibitory avoidance and escape response in the elevated T-maze, mobilizing different types of 5-HT receptors in key structures implicated in fear/anxiety.     

Dorsal raphe nucleus stimulation modulates the response of layers IV and V barrel cortical neurons in rat

The effect of dorsal raphe nucleus (DRN) electrical stimulation on response properties of layers IV and V barrel cortical neurons was studied. To assess the receptive field characteristics of cortical neurons, responses of neurons were recorded following the displacement of principal and adjacent whiskers individually or in a condition test paradigm. Then neuronal responses to the displacement of whiskers were analyzed following DRN stimulation at 0, 50, 100, 200 and 400 ms inter-stimulation intervals. Considering On responses, DRN stimulation suppressed the response magnitude of layer V neurons to principal whisker deflection, while it slightly increased that of layer IV neurons (not statistically significant). The response latency of layer IV neurons increased when DRN was stimulated 200 or 400 ms before principal whisker deflection, while the response latency of layer V was not changed. DRN stimulation had no effect on either magnitude or latency of neuronal response to the adjacent whisker deflections. We observed a decrease in the inhibitory effect of the adjacent whisker deflection on the magnitude of neuronal response to the principal whisker deflection in layer IV when DRN was stimulated 200 ms before the principal whisker deflection. Off responses did not show any significant effect of DRN stimulation. Our results suggest a modulating role for DRN in processing of the incoming information into barrel cortex. This effect might be location dependent.     

Extent of colocalization of serotonin and GABA in the neurons of the rat raphe nuclei

Previous investigations of the distribution of neurons containing both serotonin and GABA in the brainstem raphe nuclei have yielded discrepant results amongst different authors. This study attempted to clarify the distribution as well as the proportions of raphe and other brainstem neurons that contain both neurotransmitters. All the nine serotonergic cell groups known to be present in the brainstem were examined with an indirect immunofluorescence method using antibodies against serotonin and glutamic acid decarboxylase in colchicine-treated rats. Sections were incubated either simultaneously or sequentially for the two immunolabels. Brainstem neurons that were labelled for both markers were generally infrequent. Of all the serotonin cell groups in the brainstem, the nucleus raphe magnus contained the most double-labelled cells (a mean of 3.6% of a total of 625–1155 serotonin-immunoreactive cells counted in this nucleus), followed by the nucleus raphe obscurus (1.5% of a total of 220–550 serotonin-immunoreactive neurons counted). The dorsal, median and pontine raphe nuclei as well as the supralemniscal nucleus (the B9 group) contained very few double-labelled cells, which comprised a mean of 0.1–0.7% of all serotonin-immunoreactive cells in each of these nuclei. No double labelled cells were present in the caudal linear raphe nucleus or the nucleus raphe pallidus, nor in the B4 group. These results suggest that only a very small percentage of serotonergic neurons in the medullary raphe nuclei (raphe magnus and raphe obscurus) also contain GABA, whereas such cells are virtually absent in the midbrain raphe nuclei or in the non-raphe serotonergic cell groups in the brainstem.     

Enkephalinergic innervation of GABAergic neurons in the dorsal raphe nucleus of the rat

The preembedding double immunoreaction method was used to study interrelations of enkephalinergic and GABAergic neuronal elements in the dorsal raphe nucleus of the Wistar albino rat. The enkephalin-like neuronal elements were immunoreacted by the peroxidase-antiperoxidase method and silver-gold intensified, which showed strongly and was specific. The GABA-like immunoreactive neurons were immunoreacted by the peroxidase-antiperoxidase method only. GABA-like neural somata were postsynaptic to both the enkephalin-like immunoreactive and the non-immunoreactive axon terminals. The enkephalin-like immunoreactive axon terminals were also found to synapse GABA-like immunoreactive dendrites. The GABA-like immunoreactive neuronal elements were also found to receive synapses from other non-immunoreactive as well as GABA-like immunoreactive axon terminals. Almost all of the synapses appeared to be asymmetrical. Possible functional activity of interactions among the enkephalinergic, GABAergic, and serotonergic neuronal elements in the dorsal raphe nucleus are discussed.     

Morphine-induced activation of A10 dopamine neurons in the rat

The effects of intravenous administration of morphine (MOR) on the spontaneous discharge rate of dopamine (DA) neurons in the ventral tegmental area (VTA or A10) and the substantia nigra pars compacta (SNC or A9) were compared. MOR (0.5-3.5 mg/kg) produced a marked increase in the spontaneous firing of both A10 and A9 DA neurons. Naloxone (NAL) reversed the MOR effects. Acute transection of the medial forebrain bundle (MFB) did not interfere with the observed MOR effects on either A10 or A9 DA neurons. However, following chronic lesions of the MFB (6 days), A9 DA neurons were no longer responsive to MOR whereas A10 DA cells were still activated by MOR. Neither radiofrequency lesions of the dorsal raphe nucleus (DRN) nor administration of the 5-HT2 antagonist ketanserin affected the stimulatory effect of MOR on either A10 or A9 DA cells. Thus, it is confirmed that the effects of MOR on A9 DA cells depend on striatonigral feedback pathways. In contrast, it appears that the MOR-induced activation of A10 DA cells does not depend on afferents from the forebrain or on projections from the DRN, suggesting a more direct action of MOR on A10 DA cells. Microiontophoretic application of MOR or enkephalin analogues significantly increased the spontaneous activity of both A9 and A10 DA cells. However, these effects were not reversed by either iontophoretic or intravenous NAL. On the other hand, both intravenously (0.5-1.5 mg/kg) and iontophoretically administered MOR markedly suppressed the electrical activity of non-DA cells found in the vicinity of A10 DA neurons, and this effect was completely reversed by NAL. It is proposed that the MOR-induced activation of A10 DA cells could be mediated indirectly by non-DA cells.     

Degeneration of the nigral dopamine neurons after 6-hydroxydopamine injection into the rat striatum

6-Hydroxydopamine (6-OHDA) was injected into the rat striatum unilaterally. After 2-4 weeks, a marked decrease in the number of tyrosine hydroxylase-immunoreactive neuronal perikarya and dendrites was observed in the substantia nigra (SN) ipsilateral to the injection. Nissl staining showed a severe cell loss in the same region and electron microscopy revealed neuronal perikarya under degenerating process in the SN. The results showed a retrograde cytotoxic effect of 6-OHDA from the striatal terminals to their dopaminergic neuronal perikarya in the SN, and suggest the possibility that the striatum may be a primary locus in the degeneration process in Parkinson's disease.     

NK3 receptors mediate an increase in firing rate of midbrain dopamine neurons of the rat and the guinea pig

This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists, which have been proposed to possess therapeutic activity in neuropsychiatric diseases like e.g. schizophrenia. In vitro midbrain slice preparations of both species were used to record (extracellularly) the firing rates of dopamine neurons located in the substantia nigra (SN) and ventral tegmental area (VTA). Furthermore, the effect of the D2 receptor agonist quinpirole on guinea pig SN and VTA dopamine neurons was investigated. The efficacy of quinpirole in inhibiting guinea pig dopamine neuron firing activity was much less as compared to that of rat dopamine neurons, suggesting a lower dopamine D2 autoreceptor density on the guinea pig neurons. The NK3 receptor agonist senktide induced in subpopulations of rat SN (55%) and VTA (79%) and guinea pig SN (50%) and VTA (21%) dopamine neurons an increase in firing rate. In responsive neurons this effect was concentration‐dependent with EC₅₀ values of 3–5 nM (for both species). The selective NK3 receptor antagonist osanetant (100 nM) was able to partly block the senktide‐induced increase in firing rates of dopamine neurons and shifted the concentration‐response relation curves for senktide to the right (pA₂ values were ～7.5). The fractional block of the senktide responses by osanetant appeared to be larger in guinea pig dopamine neurons, indicating that osanetant is a more potent blocker of NK3 receptor‐mediated responses with noncompetitive properties in the guinea pig. Synapse 2011. © 2011 Wiley‐Liss, Inc.     

Morphological features and electrophysiological properties of serotonergic and non-serotonergic projection neurons in the dorsal raphe nucleus. An intracellular recording and labeling study in rat brain slices

The morphology and electrophysiological properties of serotonergic and non-serotonergic projection neurons in the dorsal raphe nucleus (DRN) of the rat were examined in frontal brain slices. Biocytin was injected intracellularly into the intracellularly recorded neurons. Then the morphology of the recorded neurons was observed after histochemical visualization of biocytin. The recorded neurons extending their main axons outside the DRN were considered as projection neurons. Subsequently, serotonergic nature of the neurons was examined by serotonin (5-HT) immunohistochemistry. The general form of the dendritic trees is radiant and poorly branching in both 5-HT- and non-5-HT neurons. However, the dendrites of the 5-HT neurons were spiny, whereas those of the non-5-HT neurons were aspiny. The main axons of both 5-HT- and non-5-HT neurons were observed to send richly branching axon collaterals to the DRN, ventrolateral part of the periaqueductal gray and the midbrain tegmentum. In response to weak, long depolarizing current pulses, the 5-HT neurons displayed a slow and regular firing activity. The non-5-HT neurons fired at higher frequencies even when stronger current was injected. Some other differences in electrophysiological properties were also observed between the 5-HT-immunoreactive spiny projection neurons and the 5-HT-immunonegative aspiny projection neurons.     

Effects of dizocilpine (MK-801) on rat midbrain dopamine cell activity: differential actions on firing pattern related to anatomical localization

Summary The effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) on the firing pattern of midbrain dopamine neurons were studied with single cell recording techniques in male albino rats anaesthetized with chloral hydrate. The extracellularly recorded electrical activity of single, identified dopamine neurons was studied with respect to firing rate, burst firing and regularity of firing. MK-801 (0.01–1.0 mg/kg IV) induced different effects in different subgroups of midbrain dopamine neurons. In the substantia nigra, firing rate was increased while the pattern was regularized and burst firing slightly increased. In the ventral tegmental area, firing rate and regularity of firing was also increased while effects on burst firing were bidirectional. Histological inspections revealed that neurons which responded with an increase in burst firing were mainly located in the nucleus paranigralis subdivision of the ventral tegmental area, while cells responding with a decrease were predominantly found in the nucleus parabrachialis pigmentosus subdivision. The effects of MK-801 were similar to previously described effects of phencyclidine, another non-competitive NMDA antagonist. The present effects of MK-801 might shed some light on the mechanisms involved in psychotic symptoms induced by phencyclidine and other non-competitive NMDA antagonists.     

The acute and chronic administration of (+/-)-8-hydroxy-2-(Di-n-propylamino)tetralin significantly alters the activity of spontaneously active midbrain dopamine neurons in rats: an in vivo electrophysiological study

This study examined the effect of the acute and chronic systemic administration of (+/-)-8-Hydroxy-2-(Di-n-propylamino)Tetralin(8-OH-DPAT) on the number and firing pattern of spontaneously active dopamine (DA) neurons in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in anesthetized male rats. These parameters were measured using extracellular in vivo electrophysiology. A single s.c. injection of 0.01, 0.1, or 1 mg/kg of 8-OH-DPAT did not significantly alter the number of spontaneously active SNC DA neurons compared to vehicle-treated animals (controls). The acute administration of 0.01 or 0.1 mg/kg of 8-OH-DPAT did not significantly alter, whereas the 1 mg/kg dose significantly decreased the number of spontaneously active VTA DA neurons compared to controls. The acute administration of 8-OH-DPAT significantly increased the percentage of VTA DA neurons firing in a bursting pattern. In contrast, there was a significant decrease in the percentage of SNC DA neurons firing in a bursting pattern following the acute administration of 8-OH-DPAT. The number of spontaneously active SNC DA neurons was not significantly altered by the chronic s.c. administration of 8-OH-DPAT (0.01, 0.1, or 1 mg/kg s.c.) as compared to controls. However, the chronic s.c. administration of all doses of 8-OH-DPAT significantly decreased the number of spontaneously active VTA DA neurons compared to controls. The i.v. administration of (+)-apomorphine (50 microg/kg) did not reverse the 8-OH-DPAT-induced decrease in the number of spontaneously active VTA DA neurons, suggesting that this effect is unlikely due to depolarization blockade. The percentage of VTA DA neurons exhibiting burst firing was significantly increased by 0.01 and 0.1 mg/kg, but significantly decreased by 1 mg/kg of 8-OH-DPAT. Overall, the systemic administration of 8-OH-DPAT preferentially affects the activity of spontaneously active A10 DA neurons in rats.     

Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat

The receptor-mediated axonal transport of [¹²⁵I]-labeled neurotrophins by afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [¹²⁵I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal afferent neurons retrogradely transported [¹²⁵I]neurotrophin-3 (NT-3), [¹²⁵I]nerve growth factor (NGF), and [¹²⁵I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [¹²⁵I]NT-3, [¹²⁵I]NGF, and [¹²⁵I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent neurons showed minimal accumulation of [¹²⁵I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [¹²⁵I]BDNF, [¹²⁵I]NT-3, and [¹²⁵I]NT-4, but not [¹²⁵I]NGF. The receptor specificity of neurotrophin transport was examined by applying [¹²⁵I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [¹²⁵I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [¹²⁵I]NGF was reduced only by NGF, whereas the transport of [¹²⁵I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these visceral sensory and motor neurons in vivo. J. Comp. Neurol. 393:102–117, 1998. Published 1998 Wiley-Liss, Inc.

1 This article is a US government work and, as such, is in the public domain in the United States of America.