Habenula ; Humans ; Neuralgia/therapy* ; Neurons

The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb. To probe this possibility, we developed 3-dimensional reconstruction methods for the high-resolution volumetric analysis of Hb and the mRNA levels at the given volume in normal or lipopolysaccharide (LPS)-mediated mouse model of depression. Notably, we discovered that the volume reduction was prominent in medial Hb but not in lateral Hb after LPS treatments. On the other hand, the RNA expression levels of known Hb regional markers such as Tac1 (dorsal part of medial Hb), ChAT (ventral part of medial Hb), and Tacr1 (medial and lateral Hb) were all decreased in all Hb subnuclei in LPS-injected mice. Accordingly, accurate volumetry with marker labeling was not feasible. Collectively, these established 3D analyses of mouse Hb successfully and precisely determine the volume-based changes of small brain structure, which should be applicable in a wider range of mouse models or pathological specimens.
Animals ; Brain ; Depression ; Gene Expression ; Habenula ; Hand ; Mesencephalon ; Mice ; Prosencephalon ; RNA ; RNA, Messenger ; Substance-Related Disorders

The habenula is a small and bilateral nucleus above dorsal thalamus, which contains several different types of neurons. The habenula has extensive connections with the forebrain, septum and monoaminergic nuclei in the midbrain and brainstem. Habenula is known as an 'anti-reward' nucleus, which can be activated by aversive stimulus and negative reward prediction errors. Accumulating researchs have implicated that the habenula is involved in several behaviors crucial to survival. Meanwhile, the roles of the habenula in neuropsychiatric diseases have received increasing attention. This review summaries the studies regarding the roles of habenula and the related circuits in neuropathic pain, depression, drug addiction and schizophrenia, and discusses the possibility to use the habenula as a treatment target.
Depressive Disorder ; Habenula ; Humans ; Mental Disorders ; pathology ; Mesencephalon ; Neurons ; metabolism ; Reward

Animals ; Cocaine ; pharmacology ; Habenula ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Pain Threshold ; drug effects ; Rats

AIMTo explore the types of receptors distributed in MHb and LHb.

METHODSRecording the currents of potassium channels in Hb neurons isolated from the rats 10-15 days after birth. To distinguish the types of receptors distributed in MHb and LHb by using the agonists of mu receptor DAMGO, and sigma receptor DPDPE.

RESULTSTwo types of current of K+ channels were recorded, the transient rectifier and delayed rectifier potassium channels. DAMGO or DPDPE increased the intensity of current of K+ channels.

CONCLUSIONIn MHb there was a higher density of sigma receptor, and in LHb a higher density of mu receptor distributed.

Animals ; Animals, Newborn ; Habenula ; metabolism ; Neural Pathways ; Neurons ; metabolism ; Potassium Channels ; metabolism ; Rats ; Receptors, Opioid ; metabolism

Animals ; Habenula ; cytology ; drug effects ; Male ; Microelectrodes ; Neurons ; drug effects ; physiology ; Pain ; Pregnanolone ; pharmacology ; Rats ; Rats, Wistar

Nociceptin/orphanin FQ (N/OFQ) and its receptor, nociceptin opioid peptide (NOP) receptor, are localized in brain areas implicated in depression including the amygdala, bed nucleus of the stria terminalis, habenula, and monoaminergic nuclei in the brain stem. N/OFQ inhibits neuronal excitability of monoaminergic neurons and monoamine release from their terminals by activation of G protein-coupled inwardly rectifying K⁺ channels and inhibition of voltage sensitive calcium channels, respectively. Therefore, NOP receptor antagonists have been proposed as a potential antidepressant. Indeed, mounting evidence shows that NOP receptor antagonists have antidepressant-like effects in various preclinical animal models of depression, and recent clinical studies again confirmed the idea that blockade of NOP receptor signaling could provide a novel strategy for the treatment of depression. In this review, we describe the pharmacological effects of N/OFQ in relation to depression and explore the possible mechanism of NOP receptor antagonists as potential antidepressants.
Amygdala ; Antidepressive Agents ; Brain ; Brain Stem ; Calcium Channels ; Depression ; Habenula ; Models, Animal ; Neurons ; Neuropeptides ; Opioid Peptides ; Receptors, Drug ; Septal Nuclei

AIMThe effect and possible mechanism of Melatonin (MEL) on firing rate of pain neurons in lateral habenular nucleus of rats were investigated in the experiment.

METHODSSingle extracellular firing were recorded to study the firing rate changes of pain neurons and sensitivity changes to pain stimulation induced by MEL in LHb of rats. Reverse effect of naloxone on the analgesia induced by melatonin was also observed.

RESULTSMelatonin showed the effects on the firing of pain neurons in the LHb and decreased the sensitivity of pain neurons to pain stimulation, which could be reversed by naloxone.

CONCLUSIONMelatonin can change the responses of pain neurons to pain stimulation via opioid receptor in the LHb, which might be one of analgesic mechanisms by MEL.

Analgesics ; pharmacology ; Animals ; Habenula ; drug effects ; physiology ; Male ; Melatonin ; pharmacology ; Neuralgia ; physiopathology ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

AIMTo investigate the effects and the possible mechanism of cocaine on the neurons of lateral habenular nucleus (LHb).

METHODSWe observed the effects on c-Fos protein expression in lateral habenular nucleus and medial habenular nucleus after injecting cocaine into a belly cavity and spontaneous and evoked discharge of pain-correlative unit through iontophoresis of cocaine into LHb. The delayed rectifier K+ current was recorded in the acute isolated LHb neuron in whole-cell mode.

RESULTS(1) The c-Fos protein expression was increased by cocaine treatment in LHb, but little effect in MHb. (2) Iontophoresis of cocaine into LHb increased the discharges of pain excitation unit and enhanced excitation response to noxious stimulation, but it decreased the discharges of pain inhibition unit and its responses to noxious stimulation in LHb. Cocaine inhibited the delayed rectifier K+ current.

CONCLUSIONCocaine can excite the LHb and increase its sensitivity. The probable mechanism is that cocaine inhibits the delayed rectifier K+ channels.

Animals ; Cocaine ; pharmacology ; Habenula ; drug effects ; metabolism ; physiology ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar

AIMTo explore whether dorsomedial hypothalamic nucleus (DMH) is involved in the cardiovascular responses induced by habenular nucleus (Hb) stimulation and inhibitory effect of deep peroneal nerve (DPN) stimulation on above responses or not and to analysis transmitter mechanism.

METHODSExperiments were performed on white male rabbits anesthetised with chloralose and urethan. Experimental data were collected by means of stimulating Hb and DPN, recording arterial blood pressure and ectal electrocardiogram (EECG) and microinjecting transmitter blocker.

RESULTSProminent pressor and ischemic EECG segment changes were elicited by Hb stimulation (P < 0.01) Microinjecting kynurenic acid into ipsilateral DMH had partial blocking effect on pressor and ischemic EECG-ST segment changes induced by Hb stimulation (P < 0.01). Stimulation of bilateral DPN prominently inhibited the pressor and ischemic EECG-ST changes induced by Hb stimulation (P < 0.01, P < 0.05). Microinjecting naloxone into ipsilateral DMH decreased the inhibitory effect of DPN stimulation on above cardiovascular responses elicited by Hb stimulation (P < 0.01, P < 0.05).

CONCLUSIONGlutamic acid receptor in DMH is involved in pressor and ischemic changes induced by Hb stimulation. DMH and opiate peptide receptors in DMH are involved in the inhibitory effect of DPN stimulation on pressor and ischemic changes induced by Hb stimulation.

Animals ; Cardiovascular System ; Dorsomedial Hypothalamic Nucleus ; physiology ; Electric Stimulation ; Electrocardiography ; Habenula ; physiology ; Heart Rate ; Male ; Peroneal Nerve ; physiology ; Rabbits