The effect of Pheniramine(Avil), a histaminergic-1 receptor blocking agent presently employed in treating various allergic diseases on pressor actions of norepinephring(NE) and tyramine (TR) was studied in the rabbit. Pheniramine, when given into a femoral vein with a dose(3mg/kg) enough to block H1-receptor, potentiated markedly the pressor responses of NE and TR. The pressor action of NE augmented by pheniramine was not affected by additional adminstration of debrisoquin (Drenergic neuron blocker) or phenelzine(monoamine oxidase inhibitor) or desipramine(U1-uptake blocker), or while potentiated by additional treatment with chlorisondamine(ganglionic blocker)or reserpine(catecholamine depleter). The hypertensive response of NE to phenelzine or desipramine was reinforced significantly by addition of pheniramine, but the response of NE in rabbits treated with reserpine or chlorisondamine or debrisoquin was not influenced by pheniramine-addition. Elevation of blood pressure to TR potentiated by pheniramine was attenuated significantly by reserpine treatment with chlorisondamine made the significant augmentation of pressor action to TR after pheniramine. Tyramine-induced response of blood pressure after pheniramine, but the response of blood pressure to TR caused by phenelzine or desipramine was enhanced markedly by pheniramine-treatment. From the above experimental results, it is thought that the pressor effect of NE and TR potentiated by pheniramine is similar to that of debrisoquin, i.e. the sensitization of effector cell, and that central action of pheniramine can not ruled out.
Blood Pressure ; Chlorisondamine ; Debrisoquin ; Desipramine ; Femoral Vein ; Neurons ; Norepinephrine* ; Oxidoreductases ; Phenelzine ; Pheniramine ; Rabbits ; Reserpine ; Tyramine*

Rodents exposed to a 15-min pretest swim in the forced swimming test (FST) exhibit prolonged immobility in a subsequent 5-min test swim, and antidepressant treatment before the test swim reduces immobility. At present, neuronal circuits recruited by antidepressant before the test swim remain unclear, and also less is known about whether antidepressants with different mechanisms of action could influence neural circuits differentially. To reveal the neural circuits associated with antidepressant effect in the FST, we injected desipramine or citalopram 0.5 h, 19 h, and 23 h after the pretest swim and observed changes in c-Fos expression in rats before the test swim, namely 24 h after the pretest swim. Desipramine treatment alone in the absence of pretest swim was without effect, whereas citalopram treatment alone significantly increased the number of c-Fos-like immunoreactive cells in the central nucleus of the amygdala and bed nucleus of the stria terminalis, where this pattern of increase appears to be maintained after the pretest swim. Both desipramine and citalopram treatment after the pretest swim significantly increased the number of c-Fos-like immunoreactive cells in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim. These results suggest that citalopram may affect c-Fos expression in the central nucleus of the amygdala and bed nucleus of the stria terminalis distinctively and raise the possibility that upregulation of c-Fos in the ventral lateral septum and ventrolateral periaqueductal gray before the test swim may be one of the probable common mechanisms underlying antidepressant effect in the FST.
Amygdala ; Animals ; Antidepressive Agents ; Brain ; Citalopram ; Desipramine ; Neurons ; Periaqueductal Gray ; Rats ; Rodentia ; Swimming ; Up-Regulation

PURPOSE: To compare the inhibitory effects of various tricyclic antidepressants (TCAs) on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve. MATERIALS AND METHODS: A total of forty Spraque Dawley rats (weight 300-350gm) were divided into 8 groups (n=5 in each): doxepine, amitriptyline, trimipramine, desipramine, imipramine, clomipramine, protriptyline, and prazosin treated groups. Before (baseline pressure) and 20 minutes after intravenous injection of each agent (0.1-, 1-, 10-, and 20-fold of therapeutic doses for human in each agent), the hypogastric nerves, iden tified under operative microscope, were electrically stimulated with rectangular pulses of 0.5 mseconds duration, 10 Hz, and 10 V for 10 seconds. Dose of drug administered was gradually increased in order of 0.1- to 20-fold dose. RESULTS: All drugs tested in this study caused dose-dependent inhibition of the rat intravasal pressure induced by the electrical stimulation of hypogastric nerve. Inhibitory potency of each drug was doxepine (88.5% and 96.5% at 10- and 20-fold dose)> OR = amitriptyline (76.8% and 91.8%)>clomipramine (66.7% and 74.4%)> OR =imipramine (48.2% and 67.0%)=prazosin (45.6% and 63.5%)=trimipramine (52.7% and 65.4%)> OR =desi pramine (45.3% and 49.0%)> protriptyline (18.9% and 19.9%). CONCLUSIONS: Inhibitory effects of TCAs on contractile response of the rat vas deferens to electrical stimulation of hypogastric nerve would increase in proportion to their potency of alpha1-adrenoceptor blocking actions.
Amitriptyline ; Animals ; Antidepressive Agents, Tricyclic* ; Clomipramine ; Desipramine ; Doxepin ; Electric Stimulation* ; Humans ; Imipramine ; Injections, Intravenous ; Prazosin ; Protriptyline ; Rats* ; Trimipramine ; Vas Deferens*

The frontal cortex of rat is innervated by dopaminergic pathway(mesocortical pathway) arising from ventral tegmental area. Several studies have suggested that mesocortical dopaminergic neurons may modulate the function of dopaminergic neurons at subcortical sites. The effect of lesions of the dopaminergic nerve terminals in the medial prefrontal cortex of the rat on dopamine D1 and D2 receptors within the striatum and olfactory tubercle has been investigated. Bilateral 6-hydroxy-dopamine lesions were stereotaxically placed in the medial prefrontal cortex. Animal were pretreated with desipramine to block the uptake of neurotoxin into noradrenergic terminals and to make it more selective for dopamine terminal. After 2weeks later, we examined the changes of D1 and D2 receptors in caudate-putamen and nucleus accumbens by quantitative autoradiography using the specific D1 antagonist [3H]SCH23390 and D2 antagonist [3H]spiperone. The results shows that D1 receptor at striatum was up regulated 2weeks after destruction of dopamine terminals within medial prefrontal vortex of the rat. This findings suggest that frontal cortical dopamine system may regulate the dopamine system in corpus striatum.
Animals ; Autoradiography ; Corpus Striatum ; Desipramine ; Dopamine* ; Dopaminergic Neurons ; Nucleus Accumbens ; Olfactory Pathways ; Oxidopamine* ; Prefrontal Cortex* ; Rats* ; Receptors, Dopamine* ; Ventral Tegmental Area

Changes in the levels of biogenic amines in different brain regions and the cerebrospinal fluid in rats were measured after acute or chronic treatment with tricyclic antidepressants. After single or 3 weeks' treatment with imipramine or desipramine, blocks of tissues were obtained from seven regions of the brain (frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum) immediately after collection of the cerebrospinal fluid (CSF) from the cisterna magna. The concentrations of biogenic amines and their metabolites (norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA)) in brain tissues and the CSF were measured using the high performance liquid chromatography-electrochemical detection system (HPLC-ECD). Treatment with desipramine or imipramine caused major alterations in the concentrations of central norepinephrine or 5-HT and its metabolite, respectively. Brain regional responses were variable according to the kind of tricyclic antidepressants and the duration of treatment. It is noteworthy that chronic treatment with both desipramine and imipramine caused altered hippocampal concentrations of norepinephrine and/or 5-HT and its metabolites. Striatal DOPAC concentrations were also changed after acute or chronic treatment with both drugs. These results suggest that tricyclic antidepressants altered neurotransmission according to the brain region, and the hippocampal norepinephrine and 5-HT and/or the striatal dopamine may have a significant role for the expression of antidepressant action of tricyclic antidepressants.
Animal ; Antidepressive Agents, Tricyclic/*pharmacology ; Biogenic Monoamines/*metabolism ; Brain/*drug effects/metabolism ; Desipramine/pharmacology ; Imipramine/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Antidepressants are being used as supplemental therapy in neuropathic and inflammatory pain. The mechanism of their inhibitory effect on experimental animal inflammation is not clear. Studies during the past few years clearly indicate an important role for nitric oxide (NO) in the inflammation and pain-processing system. We evaluated the effects of amitriptyline, desipramine and paroxetine on NO production in primary Schwann cell cultures. METHODS: Primary cultures of the Schwann cell were prepared from dorsal root ganglia of 1- to 3-day old Spraque-Dawley rats. Schwann cells were cultured in the presence or absence of interferon-gamma (500 ng/ml) plus tumor necrosis factor-alpha (500 ng/ml), amitriptyline, desipramine or paroxetine. Production of NO was determined in the supernatant of the culture media. RESULTS: Amitriptyline (10ng/ml), desipramine (10ng/ml) and paroxetine (10ng/ml) inhibited NO release by 29.8%, 51.4%, and 66.8%, respectively. No drug had a toxic effect on cultured cells, which was determined by an LDH assay. CONCLUSIONS: Inhibition of NO production by Schwann cells may be a mechanism by which some antidepressant medications affect inflammatory and neuropathic pain.
Amitriptyline* ; Animals ; Antidepressive Agents ; Cell Culture Techniques* ; Cells, Cultured ; Culture Media ; Desipramine* ; Ganglia, Spinal ; Inflammation ; Interferon-gamma ; Neuralgia ; Nitric Oxide* ; Paroxetine* ; Rats* ; Schwann Cells ; Tumor Necrosis Factor-alpha

OBJECTIVES: This study designed to assess the expression of phosphoCREB in rat hippocampus after chronic administration of various antidepressants in comparison with chronic administration of antipsychotic and antianxiety drugs. METHODS: Male sprague-Dawley rats(200-300g) were used for this experiment. The subjects were divided into 6groups according to specific treatment agents(paroxetine, desipramine, moclobemide, haloperidol. lorazepam, vehicl) which were administered daily for 1day, 3days, 7days, and 14days by intraperitoneal injection repectively. Brains were removed 15 minutes after the last treatment. PhosphoCREB immunoreactivity was mesured by phosphoCREB(+) cell counts in hippocampus of rats. RESULTS: Expression of phosphoCREB was significantly increased from day 3 in moclobemide group, from day 7 in paroxetine and desipramine groups, and increased most significantly from day 14 in all antidepressant-administered groups, with no increase in other tow groups(lorazepam and haloperidol group) throughout the experiment and even after 14 days of treatment. CONCLUSION: These result suggest that increased expression of phosphoCREB after chronic administration of antidepressants, not of antipsychotic or antianxiety drugs, demonstrates pharmacological specificity of antidepressant treatment in rat hippocampus regardless of their receptor preference.
Animals ; Antidepressive Agents ; Brain ; Cell Count ; Cyclic AMP* ; Desipramine ; Haloperidol ; Hippocampus* ; Humans ; Injections, Intraperitoneal ; Lorazepam ; Male ; Moclobemide ; Paroxetine ; Rats* ; Rats, Sprague-Dawley ; Response Elements* ; Sensitivity and Specificity

The central dopaminergic receptor is believed to suppress the cardiovascular system So it may be involved in the blood pressure regulation But, it's action is still controversial. Furthermore, the mechanisms involved in the central dopaminergic receptor-induced blood pressure regulation is unclear. So, present study was performed in order to clarify the effects of central dopaminergic receptor and to investigate the mechamisms involved in it. Lisuride a D2-receptor agonist, and clonidine, a alpha2-receptor agonist, were administered into lateral ventricle in rat and the changes of blood pressure were compared The results were as follows; 1. Intracerebroventricular administration of lisuride amd clonidine from 0.3 ug to 10 ug elicited dose related decrease of blood pressure and heart rate. The potencies were similar in both drugs. 2. Centrally administered sulpiride, a D2-antagonist, blocked only the lisuride-induced hypotension while the clonidine induced hypotension was blocked only by centrally adrninistered tolazoline, a alpha2-antagonist. Intravenous administration of both antagonists elicited no or minimal attenuabon of agonists effects. 3. After desipramine pretreatment, which increases the norepinephrine concentration lisuride elicited somewhat further decrease of blood pressure than normal, while clonidine administration caused rather increase in blood pressure. 4. After chemical sympathectomy by 6-hydroxydopamine, lisuride administration still elicited strong suppression of blood pressure. From thses above results, it is concluded that central dopaminergic receptor activation decrease the blood pressure. Suppression of the norepinephrine release at the sympathetic nerve terminal is not related with central dopaminergic receptor induced hypotension.
Administration, Intravenous ; Animals ; Blood Pressure ; Cardiovascular System* ; Clonidine ; Desipramine ; Heart Rate ; Hypotension ; Lateral Ventricles ; Lisuride ; Norepinephrine ; Oxidopamine ; Rats ; Sulpiride ; Sympathectomy, Chemical ; Tolazoline

BACKGROUND & OBJECTIVE: Stereotaxic injection of 6-hydroxydopamine(6OHDA) into the ventral midbrain is the most commonly used Parkinsonian animal model. In the presence of norepinephrine(NE) uptake blockers, 6OHDA is believed to be selectively toxic to the dopamine(DA) system. However, it was observed in this model that there is a massive fiber degeneration in the fornix, where there are no known DA fibers. There are NE fibers in the fornix arising from the locus ceruleus (LC) terminating in the cerebral cortex including hippocampus. The study was done to examine whether there is a change in the NE system and characterize the neurochemical nature of the previously demonstrated degenerating fornix fibers. METHODS: 6OHDA was injected stereotaxically into the unilateral ventral midbrain in desipramine pretreated rats. DA and NE were measured in the striatum, cortex, hippocampus, and LC. Silver staining was done to demonstrate degenerating neurons and nerve terminals. Immunohistochemistry using tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was done to demonstrate catecholamine neurons and nerve fibers. RESULTS: DA was markedly depleted in the ipsilateral striatum. NE was decreased in the striatum, cortex, and hippocampus, but not in the LC. Silver staining showed massive fiber degeneration in the fornix, but did not show degenerating neurons in the LC. TH and DBH Immunohistochemistry failed to show catecholaminergic fibers in the fornix. There was no side difference on immunostaining in the LC neurons. CONCLUSION: 6OHDA Parkinson model does not make selective lesion to the DA system, and damages ascending NE fibers. Neuronal cell bodies in the LC remain intact in this model. The neurochemical nature of the degenerating fornix fibers is not clearly characterized.
Animals ; Cerebral Cortex ; Desipramine ; Dopamine beta-Hydroxylase ; Hippocampus ; Immunohistochemistry ; Locus Coeruleus ; Mesencephalon ; Models, Animal ; Models, Theoretical* ; Nerve Fibers ; Neurons ; Oxidopamine* ; Parkinsonian Disorders* ; Rats ; Silver Staining ; Tyrosine 3-Monooxygenase

The purpose of the present was devalopment of a new pain assessment model that recorded in free moving rats to eliminte of anesthetic agents in orofacial area. Antinociceptive effects and mechanisms of tricyclic antidepressants is also investigated. Fifty-five male Wistar rats (400-500gm) were anesthetized with an intraperitoneal injection of urethane (500microgram/kg) and pentobarbital sodium ((20microgram/kg). Anesthetized rats mounted in a sterotaxic instrument and a guide cannula was implanted in the lateral ventricle. The Cordinates were 0.8mm posterior to bregma, 1.5mm lateral from midline and 0.4mm ventral from the skull. Stimulating electrodes implanted in the incisor plup and recording electrodes were inserted into the belly of digastric musle. Stimulating and recording eletodes were led subcutaneously to miniature cranial connector sealed on the top of the skullwhit acrylic resin. Jaw opening reflex (JOP) was used a pian assessment. Jaw opening reflex is elicted by noxious stimulation of the incisor and is quantified by the magnitude of electromyogram of digastric muscle(dEMG). After a 48hours recovery period from surgery. JOR was recorded in free moving rats. Electrcal shock (200 sec duration, 0.5-2mA intensity, 0.5Hz) were delivered to the dental plup. Twenty subsequent electromyograms were recorded from digastric music in free moving rats. After intraperitioneal injection of 15microgram/kg impramine or nortriptyline dEMG was suppressed to 64+/-6 or 56+/-8% of the control. Intraperitioneal injection of 30microgram/kg desipramine, impramine or nortriptyline dEMG respectively to 44+/-9, 15+/-4, or 16+/-3% of the control. After intravenous injection of 12microgram/kg desipramine, imipramine or nortriptyline, dEMG was suspressed to 73 7, 50 4, or 66 7% of the control. Intravenous injection of 18microgram/kg desipramine, imipramine or nortriptyline suppressed dEMG respectively to 57+/-6, 12+/-3 or 6+/-2% of the control. To investigate the central mechanisms of antinociception of nortriptyline, naloxne, opioid receptor antagonist, methysergide, and phentolamine inhibited suppression of dEMG by intravenous injection of 18microgram/kg notriptyline from 7+/-2 to 47+/-9, from 4+/-2 to 24+/-6, and from 4+/-1 to 51+/-7% of the control resectively. these results suggest that antidepressant agents be to modulate pain transmission in orofacial area. The analgesia produced by intraperitioneal and intraventous injection of antidepressants seems to be mediated by multipule pathways such as descending pain inhibitory system.
Analgesia ; Anesthetics ; Animals ; Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Catheters ; Desipramine ; Electrodes ; Humans ; Imipramine ; Incisor ; Injections, Intraperitoneal ; Injections, Intravenous ; Jaw ; Lateral Ventricles ; Male ; Methysergide ; Music ; Nortriptyline ; Pain Measurement ; Pentobarbital ; Phentolamine ; Rats* ; Rats, Wistar ; Receptors, Opioid ; Reflex* ; Shock ; Skull ; Urethane