Serotonin-containing Neurons Research Articles

The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines

The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines “2C series” in monoaminergic neurons. After the exposure to “2C series”, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells. Single dose exposure to “2C series” for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 µM) > 2C-T-2 (150 µM), 2C-T-4 (200 µM) > 2C-I (250 µM) in CATH.a cells and 2C-T-7, 2C-I (150 µM) > 2C-T-2 (250 µM) > 2C-C, 2C-T-4 (300 µM) in B65 cells. The “2C series”-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50: ≥ 1–2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of “2C series”. The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes. The 2,5-dimethoxy-substitution of “2C series” induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons.

Targeting Serotonin1A Receptors for Treating Chronic Pain and Depression.

The association of chronic pain with depression is becoming increasingly recognized. Treating both the conditions together is essential for an effective treatment outcome. In this regard, it is important to identify a shared mechanism involved in the association of chronic pain with depression. Central serotonin (5-hydroxytryptamine; 5-HT) neurotransmission has long been known to participate in the processing of signals related to pain. It also plays a key role in the pathogenesis and treatment of depression. Although functional responses to serotonin are mediated via the activation of multiple receptor types and subtypes, the 5-HT1A subtype is involved in the processing of nociception as well as the pathogenesis and treatment of depression. This receptor is located presynaptically, as an autoreceptor, on the perikaryon and dendritic spines of serotonin-containing neurons. It is also expressed as a heteroreceptor on neurons receiving input from serotonergic neurons. This arti-cle targets the 5-HT1A receptors to show that indiscriminate activation of pre and postsynaptic 5-HT1A receptors is likely to produce no therapeutic benefits; biased activation of the 5-HT heteroreceptors may be a useful strategy for treating chronic pain and depression individually as well as in a comorbid condition.

Immunohistochemical and biochemical evidence for the presence of serotonin-containing neurons and nerve fibers in the octopus arm.

The octopus arm contains a tridimensional array of muscles with a massive sensory-motor system. We herein provide the first evidence for the existence of serotonin (5-HT) in the octopus arm nervous system and investigated its distribution using immunohistochemistry. 5-HT-like immunoreactive (5-HT-lir) nerve cell bodies were exclusively localized in the cellular layer of the axial nerve cord. Those cell bodies emitted 5-HT-lir nerve fibers in the direction of the sucker, the intramuscular nerves cords, the ganglion of the sucker, and the intrinsic musculature. Others 5-HT-lir nerve fibers were observed in various tissues, including the cerebrobrachial tract, the skin, and the blood vessels. 5-HT was detected by high-performance liquid chromatography in various regions of the octopus arm at levels matching the density of 5-HT-lir staining. The absence of 5-HT-lir interconnections between the cerebrobrachial tract and the other components of the axial nerve cord suggests that two types of 5-HT-lir innervation exist in the arm. One type, which originates from the brain, may innervate the periphery through the cerebrobrachial tract. Another type, which originates in the cellular layer of the axial nerve cord, may form an intrinsic network in the arm. In addition, 5-HT-lir fibers likely emitted from the neuropil of the axial nerve cord were found to project into cells showing staining for peripheral choline acetyltransferase, a marker of sensory cells of the sucker. Taken together, these observations suggest that intrinsic 5-HT-lir innervation may participate in the sensory transmission in the octopus arm.

The roles of the orbitofrontal cortex via the habenula in non-reward and depression, and in the responses of serotonin and dopamine neurons

Cortical regions such as the orbitofrontal cortex involved in reward and in non-reward and which are implicated in depression, and the amygdala, are connected to the habenula via the striatum and pallidum, and via subcortical limbic structures. The habenula in turn projects to the raphe nuclei, the source of the serotonin-containing neurons that project to the forebrain. It is proposed that this provides a route for cortical signals related to reward, and to not obtaining expected rewards, to influence the serotonin-containing neuronal system that is influenced by many antidepressant treatments. This helps to provide a more circuit-based understanding of the brain mechanisms related to depression, and how some treatments influence this system. The habenula also projects via the rostromedial tegmental nucleus to the dopamine-containing neurons, and this, it is proposed, provides a route for reward prediction error signals and other reward- and punishment-related signals of cortical and striatal origin to influence the dopamine system.

Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

Numerous studies suggest (1) that a major physiological role of brain serotonin-containing neurons is to modulate sex steroid-driven behaviour such as sex and aggression, (2) that sex steroids influence brain serotonergic neurotransmission and (3) that brain serotonergic neurotransmission displays sexual dimorphism. Such observations indicate that an important task for brain serotonin is to either enhance or counteract sex differences in behaviour. To test this hypothesis, we explored the effect of short-term serotonin depletion on the behaviour of adult male and female rats in a behavioural paradigm in which males and females have been shown to behave differently, i.e. the elevated plus maze. Two rounds of testing of untreated Wistar rats confirmed the previous observation that females make more entries into open arms (round 1, p = 0.001; round 2, p = 0.008) and spend more time on these arms (round 1, p ≤ 0.001; round 2, p = 0.006) than males; in addition, males displayed fewer entries into closed arms upon habituation, i.e. at the second round (p ≤ 0.001) than did females. Administration of the tryptophan hydroxylase inhibitor para-chloro-phenylalanine, at a regimen (300mg/kg/day for 3days), markedly reducing brain content of serotonin, enhanced entries upon open arms (p = 0.01) and time spent on open arms (p = 0.004) in males but exerted no such effects in females (p = 0.9 and p = 0.9, respectively); moreover, it reduced entries into closed arms in females (p ≤ 0.001) but not in males (p = 0.1). Serotonin depletion abolishing the sex differences observed at baseline supports the theory that serotonin aids to uphold certain sex differences in behaviour.

Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways

Decrease of γ-aminobutyric acid (GABA)-mediated neurotransmission in the dorsomedial hypothalamus (DMH) evokes instinctive fear-like responses. The aim of the present study was to investigate the involvement of the serotonin (5-HT)- and norepinephrine-mediated pathways of the endogenous pain inhibitory system, including the dorsal raphe nucleus (DRN) and the locus coeruleus (LC), in the defensive responses and antinociceptive processes triggered by the blockade of GABAergic receptors in the DMH. The intra-hypothalamic microinjection of the GABAA receptor antagonist bicuculline (40 ng/200 nL) elicited elaborate defensive behaviours interspersed with exploratory responses. This escape behaviour was followed by significantly increased pain thresholds, a phenomenon known as fear-induced antinociception. Furthermore, at 5 and 14 days after DRN serotonin-containing neurons were damaged using the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), the frequency and duration of alertness and escape behaviour evoked by the GABAA receptor blockade in the DMH decreased, as well as fear-induced antinociception. Pre-treatment with the non-selective 5-HT receptor antagonist methysergide, the 5-HT2A/2C receptor antagonist ketanserin and the 5-HT2A receptor selective antagonist R-96544 in the LC also decreased fear-induced antinociception, without significant changes in the expression of defensive behaviours. These data suggest that the serotonergic neurons of the DRN are directly involved in the organisation of defensive responses as well as in the elaboration of the innate fear-induced antinociception. However, serotonin-mediated inputs from the NDR to the LC modulate only fear-induced antinociception and not the defensive behaviours evoked by GABAA receptor blockade in the DMH.

A minimal model for a slow pacemaking neuron

We have constructed a phenomenological model for slow pacemaking neurons. These are neurons that generate very regular periodic oscillations of the membrane potential. The examples of these neurons are serotonin-containing neurons from the raphe nuclei, noradrenergic neurons located in the pontine nucleus locus coeruleus (LC) and dopaminergic neurons from the substantia nigra pars compacta. Many of these neurons also differentially respond to various types of stimulation. In particular, stimulation by injecting a current into the cell body (applied somatic depolarization) is expected to elicit bursting similar to stimulation by inputs from other neurons (synaptic currents), but it does not. We have separated the most important property of the neuron that allows for the differential responses (see Fig. ​Fig.1).1). Our model is based on FitzHugh-Nagumo (FHN) oscillator and implements a nonlinearity introduced by a current that depends on an ion concentration. The nonlinearity is crucial for such differentiation. We have explicitly shown that when the nonlinear activation function is replaced by a linear dependence, the model responds similarly to all stimuli and shows very little frequency variation. These are the properties of the classical FHN oscillator. Thus, the new nonlinear dependence allows for differentiating responses to various stimuli. Figure 1 The NMDAR activation elevates the frequency, while the applied depolarization blocks oscillations. The voltage time-series are shown in response to square pulses of the applied depolarization (A) and NMDAR activation (B). In the DA neuron, an SK-type Ca2+-dependent K+ current provides the necessary nonlinearity. Presumably, the same current works in serotonergic neurons. No data is available for other neurons, and the SK current may not be the only current that differentiates the responses. The mechanism works for other currents with a sigmoidal activation function. In fact, any function that starts flat and then sharply increases its slope works. The saturation part of the sigmoidal dependence is not necessary for the frequency responses. The current may depend on ion concentration, on the voltage, or on both variables. This further expands the applicability of our results to neurons expressing various currents. Therefore, in a wide class of neurons, the nonlinearity of a conductance will cause distinct responses to stimuli.

P-Hydroxyamphetamine causes prepulse inhibition disruption in mice: Contribution of serotonin neurotransmission

p-Hydroxyamphetamine (p-OHA) has been shown to have a number of pharmacological actions, including causing abnormal behaviors such as increased locomotor activity and head-twitch response in rodents. We have recently reported that intracerebroventricular (i.c.v.) administration of p-OHA dose-dependently induces prepulse inhibition (PPI) disruption in mice, which is attenuated by pretreatment with haloperidol, clozapine or several dopaminergic agents. Haloperidol and clozapine have affinities for serotonergic (especially 5-HT2A) receptors. To investigate the involvement of the central serotonergic systems in p-OHA-induced PPI disruption, herein we tested several serotonergic agents to determine their effects on p-OHA-induced PPI disruption. p-OHA-induced PPI disruption was attenuated by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, a neurotoxin which targets serotonin-containing neurons) and p-chlorophenylalanine (PCPA, a serotonin synthesis inhibitor). p-OHA-induced PPI disruption was also attenuated by pretreatment with ketanserin (a 5-HT2A/2C receptor antagonist) and MDL100,907 (a selective 5-HT2A receptor antagonist). These data suggest that p-OHA-induced PPI disruption may involve increased serotonin release into the synaptic cleft, which then interacts with the post-synaptic 5-HT2A receptor.

Involvement of Spinal Serotonin Receptors in Electroacupuncture Anti-Hyperalgesia in an Inflammatory Pain Rat Model

We previously showed that electroacupuncture (EA) activates medulla-spinal serotonin-containing neurons. The present study investigated the effects of intrathecal 5,7-dihydroxytryptamine creatinine sulfate, a selective neurotoxin for serotonergic terminals, the 5-hydroxytryptamine 1A receptor (5-HT1AR) antagonist NAN-190 hydrobromide and the 5-HT2C receptor (5-HT2CR) antagonist SB-242,084 on EA anti-hyperalgesia. EA was given twice at acupoint GB30 after complete Freund's adjuvant (CFA) injection into hind paw. CFA-induced hyperalgesia was measured by assessing hind paw withdrawal latency (PWL) to a noxious thermal stimulus 30 min post-EA. Serotonin depletion and the 5-HT1AR antagonist blocked EA anti-hyperalgesia; the 5-HT2CR antagonist did not. Immunohistochemical staining showed that spinal 5-HT1AR was expressed and that 5-HT2CR was absent in naive and CFA-injected animals 2.5 h post-CFA. These results show a correlation between EA anti-hyperalgesia and receptor expression. Collectively, the data show that EA activates supraspinal serotonin neurons to release 5-HT, which acts on spinal 5-HT1AR to inhibit hyperalgesia.

P02-339 - Spect imaging of the serotonin transporter using a novel ligand - 123-I mZIENT - in human subjects - a dosimetry and biodisortribution study

Levels of serotonin in the body are regulated by the serotonin transporters (SERT), which are predominantly located on the presynaptic terminals of serotonin-containing neurons. Alterations in the density of SERT have been implicated in the pathophysiology of many neuropsychiatric disorders.AimTo evaluate 123-I mZIENT (2(S)-[(S)-2b-carbomethoxy-3b-[3′-((Z)-2-iodoethenyl)phenyl]nortropane), a novel radiopharmaceutical for imaging SERT. The bio-distribution of the radiopharmaceutical in humans was investigated and dosimetry performed.MethodsThe study includes three healthy volunteers and three patients receiving SSRIs. Whole body images obtained on a gamma camera at 10 minutes, 1, 2, 3, 6, 24 and 48 hours post administration. Dosimetry was performed. ROIs were drawn over the brain, heart, kidneys, liver, lungs, salivary glands, spleen, thyroid and intestines. Blood was sampled at 5, 15, & 30 minutes and 1, 2, 3, 6, 24 and 48 hours post administration. Urine was collected at 1, 2, 3, 4, 6, 24 and 48 hours. Brain SPECT images were obtained using a neuroSPECT scanner at 4 hours, evaluated visually and analysed using ROI analysis.ResultsHigh quality SPECT images can be obtained after 100–150 MBq 123-ImZEINT. Regional brain uptake was observed in midbrain and basal ganglia in healthy volunteers, consistent with the known distribution of SERT. Biodistribution images demonstrated highest uptake in the lungs, brain, liver and intestines. The effective dose was within range of other commonly used ligands and is acceptable for clinical imaging.Conclusion123-ImZIENT is a promising agent for imaging SERT in humans with acceptable dosimetry.

Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice

BackgroundTo secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response.Methodology/Principal FindingsUsing en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25–50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice.ConclusionsThese results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers.

Nucleus raphé pallidus participates in midbrain-medullary cardiovascular sympathoinhibition during electroacupuncture

We have shown that electroacupuncture (EA) inhibits sympathoexcitatory rostral ventrolateral medulla (rVLM) neurons and reflex responses following activation of a long-loop pathway in the arcuate nucleus and ventrolateral periaqueductal gray (vlPAG). Additionally, EA at P 5-6 acupoints (overlying the median nerve) activates serotonin-containing neurons in the nucleus raphé pallidus (NRP), which, in turn, inhibit rVLM neurons. Although direct projections from the vlPAG to the rVLM exist, it is uncertain whether an indirect pathway through the NRP serves an important role in vlPAG-rVLM cardiovascular modulation. Therefore, the splanchnic nerve (SN) was stimulated to induce cardiovascular sympathoexcitatory reflexes, and EA was applied at P 5-6 acupoints in α-chloralose-anesthetized cats. A single-barreled recording electrode was inserted into the NRP or rVLM. Microinjection of DL-homocysteic acid (DLH) into the vlPAG increased the NRP neuronal response to SN stimulation (5 ± 1 to 12 ± 2 spikes/30 stim). Likewise, EA at P 5-6 for 30 min increased the NRP response to SN stimulation (3 ± 1 to 10 ± 2 spikes/30 stim), an effect that could be blocked by microinjection of kynurenic acid (KYN) into the caudal vlPAG. Furthermore, the reflex increase in blood pressure induced by application of bradykinin to the gallbladder and the rVLM cardiovascular presympathetic neuronal response to SN stimulation was inhibited by injection of DLH into the vlPAG, a response that was reversed by injection of KYN into the NRP. These results indicate that EA activates the vlPAG, which excites the NRP to, in turn, inhibit rVLM presympathetic neurons and reflex cardiovascular sympathoexcitatory responses.

The role of dorsal raphe nucleus serotonergic and non-serotonergic neurons, and of their receptors, in regulating waking and rapid eye movement (REM) sleep

Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches it is currently accepted that serotonin (5-HT) functions to promote waking (W) and to inhibit rapid-eye movement sleep (REMS). The serotonin-containing neurons of the dorsal raphe nucleus (DRN) provide part of the serotonergic innervation of the telencephalon, diencephalon, mesencephalon and rhombencephalon of laboratory animals and man. The DRN has been subdivided into several clusters on the basis of differences in cellular morphology, expression of other neurotransmitters and afferent and efferent connections. These differences among subpopulations of 5-HT neurons may have important implications for neural mechanisms underlying 5-HT modulation of sleep and waking. The DRN contains 5-HT and non-5-HT neurons. The latter express a variety of substances including dopamine, γ-aminobutyric acid (GABA) and glutamate. In addition, nitric oxide and a number of neuropeptides have been characterized in the DRN. Available evidence tends to indicate that non-5-HT cells contribute to the regulation of the activity of 5-HT neurons during the sleep-wake cycle through local circuits and/or their mediation of the effects of afferent inputs. Mutant mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of REMS than their wild-type couterparts. 5-HT(2A) and 5-HT(2C) receptor knockout mice show a significant increase of W and a reduction of slow wave sleep that is related, at least in part, to the increased release of norepinephrine and dopamine. A normal circadian sleep pattern is observed in 5-HT(7) receptor knockout mice; however, the mutants spend less time in REMS. Local microinjection of 5-HT(1B), 5-HT(2A/2C), 5-HT(3) and 5-HT(7) receptor agonists into the DRN selectively suppresses REMS in the rat. In contrast, microinjection of 5-HT(1A) receptor agonists promotes REMS. Similarly, local administration of the melanin-concentrating hormone or the GABA(A) receptor agonist muscimol produces an increase of REMS in the rat. Presently, there are no data on the effect of local infusion into the DRN of noradrenergic, dopaminergic, histaminergic, orexinergic and cholinergic agonists on sleep variables in laboratory animals.

Brainstem reticulospinal neurons are targets for corticotropin-releasing factor-Induced locomotion in roughskin newts

Stress-induced release or central administration of corticotropin-releasing factor (CRF) enhances locomotion in a wide range of vertebrates, including the roughskin newt, Taricha granulosa. Although CRF's stimulatory actions on locomotor behavior are well established, the target neurons through which CRF exerts this effect remain unknown. To identify these target neurons, we utilized a fluorescent conjugate of CRF (CRF-TAMRA 1) to track this peptide's internalization into reticulospinal and other neurons in the medullary reticular formation (MRF), a region critically involved in regulating locomotion. Epifluorescent and confocal microscopy revealed that CRF-TAMRA 1 was internalized by diverse MRF neurons, including reticulospinal neurons retrogradely labeled with Cascade Blue dextran. In addition, we immunohistochemically identified a distinct subset of serotonin-containing neurons, located throughout the medullary raphé, that also internalized the fluorescent CRF-TAMRA 1 conjugate. Chronic single-unit recordings obtained from microwire electrodes in behaving newts revealed that intracerebroventricular (icv) administration of CRF-TAMRA 1 increased medullary neuronal firing and that appearance of this firing was associated with, and strongly predictive of, episodes of CRF-induced locomotion. Furthermore, icv administered CRF-TAMRA 1 produced behavioral and neurophysiological effects identical to equimolar doses of unlabeled CRF. Collectively, these findings provide the first evidence that CRF directly targets reticulospinal and serotonergic neurons in the MRF and indicate that CRF may enhance locomotion via direct effects on the hindbrain, including the reticulospinal system.

Serotonin and Sleep: Molecular, Functional, and Clinical Aspects

Serotonin and Sleep: Molecular, Functional, and Clinical Aspects

Development of the serotoninergic system in the central nervous system of a shark, the lesser spotted dogfish Scyliorhinus canicula

Chondrychthyans (cartilaginous fishes) are key to understanding the ancestral gnathostome condition since they provide an outgroup to sarcopterygians and actinopterygians. To gain comparative knowledge about the development of the vertebrate serotoninergic systems, we studied by immunohistochemistry the origin, spatiotemporal organization, and migration patterns of serotonin-containing neurons and the growth of axonal pathways in the central nervous system of a shark, the lesser spotted dogfish. Hindbrain serotonin-immunoreactive cells arose close to the floor plate and most populations migrated ventrally and mediolaterally to form the various raphe and reticular groups. The order of appearance of serotoninergic populations in the rhombencephalon and spinal cord (first the superior groups and then the inferior and spinal populations) roughly matched with that reported in other vertebrates but important differences were noted in the formation of prosencephalic groups in fishes. In addition to preoptic and hypothalamic areas, serotoninergic cerebrospinal fluid-contacting cells were observed in the isthmus (raphe dorsalis anterioris). Transient serotonin-immunoreactive cells were noted in the pineal organ, habenula, and pretectum. Further, we provide a revised anatomical framework for reticular and raphe serotoninergic populations considering their origin and segmental organization. Two distinct phases of development of the serotoninergic innervation were distinguished, that of the formation of the main axonal pathways and that of the branching of fibers. The development of main serotoninergic ascending pathways in dogfish was notably similar to that described in mammals. Our findings suggest the conservation of developmental patterns in serotoninergic systems and enhance the importance of elasmobranchs for understanding the early evolution of this system in vertebrates.

Inactivation of median preoptic nucleus causes c-Fos expression in hypocretin- and serotonin-containing neurons in anesthetized rat

The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurons including sleep-active GABAergic neurons and is involved in the regulation of nonREM/REM sleep. The hypocretinergic (HCRT) neurons of the perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) are mostly active during waking and have been implicated in the regulation of arousal. MnPN GABAergic neurons project to the PF-LHA and DRN. It is hypothesized that MnPN promotes sleep by inhibiting multiple arousal systems including HCRT and other wake-active neurons within the PF-LHA and 5-HT neurons in the DRN. We examined the effects of inactivation of MnPN neurons by locally microinjecting 0.2 µl of 1 mM or 10 mM solutions of a GABA A receptor agonist, muscimol, into the MnPN on Fos expression (Fos-IR) in the PF-LHA neurons including HCRT neurons and 5-HT neurons in the DRN in anesthetized rats. Compared to artificial cerebrospinal fluid control, microinjection of muscimol into the MnPN resulted in significantly higher percentages of HCRT and non-HCRT neurons in the PF-LHA and 5-HT neurons in the DRN that exhibited Fos-IR. The percentage of melanin-concentrating hormone (MCH)+/Fos+ neurons in the PF-LHA did not change after muscimol treatments. These results support a hypothesis that the activation of MnPN neurons contributes to the suppression of wake-promoting systems including HCRT and other unidentified neurons in the PF-LHA and 5-HT neurons in the DRN. These results also suggest that MCH neurons may not be under MnPN inhibitory control. These findings are consistent with a hypothesized role of MnPN in sleep regulation.

Localization of serotonin transporter mRNA in the CNS ofLymnaea stagnalis

The serotonin transporter, SERT, is reported as a key molecule that regulates serotonergic neurotransmission. In the present study, we analyzed the localization of Lymnaea SERT (LymSERT) mRNA-containing neurons by in situ hybridization using frozen sections of the central nervous system (CNS) of Lymnaea. To precisely demonstrate the distribution of LymSERT mRNA-containing neurons, colocalization with serotonin immunoreactivity was also examined. The results showed that LymSERT mRNA was constitutively expressed and localized in the serotonin-containing neurons in the CNS.

Menace: Methamphetamine in Rural Communities

Over 35 million persons worldwide regularly use or abuse methamphetamines (WHO, 2008). This statistic then puts methamphetamine as the second most common abused drug after cannabis. Methamphetamine addiction differs from other illicit drugs such as cocaine or heroin. Drug addicts describe this drug as “one hit, one hook.” This defining characteristic of crystal methamphetamine is that addiction appears to occur upon first use. Methamphetamine use causes multiple anatomical defects in the brain and damages the frontal decision-making center. The action of the drug on the dopamine and serotonin-containing neurons creates false circuits. Even upon discontinuation of the drug, antipsychotic treatments are often required (National Institute of Drug Abuse, 2006). The consequences of these illicit drugs can be the destruction of families, depression, anxiety, paranoia, aggression, cardiovascular events, sexual abuse, and child endangerment (Grant, Kelley, Agrawal, Meza, Meyer, & Romberger, 2007). DEA (2008) statistics report that 20 percent of the meth labs seized last year had children present on site. Children are even more vulnerable to the life time consequences of the toxins of methamphetamines on both pulmonary and neurological systems. Methamphetamines are at the epicenter of circles of addiction that cause health consequences throughout our global community.

Comparison of projections of the dorsal and median raphe nuclei, with some functional considerations

Abstract It is well established that the brainstem contains discrete groups of serotonin-containing neurons with extensive axonal processes that distribute throughout the neuroaxis. Serotonergic neurons have been implicated in a range of functions including sleep/wakefulness, feeding, affect/emotion, thermoregulation, and cognitive behaviors. We describe the projections and some functional properties of the two major serotonergic cell groups of the brain, the dorsal raphe (DR) and the median raphe (MR) nuclei. DR fibers distribute widely throughout the forebrain to dopamine-containing nuclei of the ventral midbrain, the lateral hypothalamus, the midline thalamus, amygdala, the dorsal and ventral striatum and adjoining regions of the basal forebrain, and most of the cortex. By contrast with DR, MR is a midline/paramidline system of projections. Specifically, MR fibers mainly distribute to forebrain structures lying on or close to the midline including the medial mammillary and supramammillary nuclei, posterior and perifornical nuclei of the hypothalamus, midline and intralaminar nuclei of the thalamus, lateral habenula, medial zona incerta, diagonal band nuclei, septum and hippocampus. Overall, MR projections to the cortex are light. With few exceptions, DR and MR project to separate, non-overlapping regions of the forebrain — or, in effect, DR and MR share the serotonergic innervation of the forebrain. We discuss roles for DR in sleep/wake control, feeding/appetite and mood/affect, and for MR in the control of electroencephalographic (EEG) activity of the hippocampus — or states of hippocampal EEG desynchronization.