Changes in c-Fos Expression in the Forced Swimming Test: Common and Distinct Modulation in Rat Brain by Desipramine and Citalopram

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.

[Comparison of desipramine and sertraline in the treatment of depression in patients suffering from alzheimer disease]

As depression is a common comorbid disorder with Alzheimer disease, it is important to recognize treatments with more effective and less adverse effects. This study has been devised to comparatively evaluate the effects of desipramine and sertraline in this patients. In this single blind clinical trial study, during January 2005 to April 2008, 63 outpatients in Ibn-e-Sina and Ghaem University hospitals in Mashhad city [north eastern part of Iran] were randomly allocated to two groups: 29 cases were treated by desipramine and 34 patients were treated with sertraline [both 25mg/day and if needed up to 150 mg/day]. Patients were assessed at 2, 4, 8 and 12[th] week by PDRS, HRDS and MMSE and side effects of medications. Changes in mood with HRDS and CSDD have shown that sertraline was effective in all weeks [p<0.05]. In contrast, desipramine had no therapeutic effect except in the 12[th] week according to HRDS scale [p<0.05]. Differences between the groups were significant [p=0.02]. Differences between daily activating scales regarding PDRS in 8[th] and 12[th] week in desipramine group were statistically meaningful [p<0.05], but not in the sertraline group and between the two groups. Also, cognitive changes by MMSE were not significant in the two groups and between the two groups. Sertraline is more effective than desipramine in the treatment of depression in patients who suffer from alzheimer disease, but they are ineffective on cognitive problems

Possible role of citalopram and desipramine against sleep deprivation-induced anxiety like-behavior alterations and oxidative damage in mice.

Sleep is an essential physiological process for maintaining physical, mental, and emotional health. Sleep deprivation and associated disorders like depression and anxiety are one of the major problems now-days. The present study was designed to explore the neuroprotecitve effect of citalopram and desipramine on 72 hr sleep deprivation-induced behavioral alterations and oxidative damage in mice. Various behavioral tests (plus maze, zero maze, mirror chamber, actophotometer), body weight followed by oxidative parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. Treatment with citalopram (5 and 10 mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) for 5 days significantly improved locomotor activity, anti-anxiety like behavior in all paradigms tasks (mirror chamber, plus maze, zero maze) as compared to control (72 hr sleep-deprived). Biochemically, citalopram and desipramine treatment significantly restored depleted reduced glutathione, catalase activity, attenuated raised lipid peroxidation and nitrite level as compared to control (72 hr sleep-deprived) animals. Results of present study suggest that citalopram (5 and 10mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) have neuroprotective effect against sleep deprivation-induced behavior alteration and oxidative damage in mice.

Desipramine versus ropivacaine for prolonged cutaneous analgesia in rats

Desipramine is a tricyclic anti depressant that has a potent local anesthetic activity comparable to ropivacaine. In keeping with the objective of identifying drugs for prolonged cutaneous analgesia, we compared the cutanaous analgesic effectiveness of desipramine and ropivacaine in rats. Rats were subcutaneously injected in shaved dorsal skin. The skin wheal raised after injection of 0.6 ml of various concentrations of either desipramine or ropivacaine with and without epinephrine 1,200,000 was marked. Inhibition of the Cutaneous trunci muscle reflex was evaluated quantitatively by the fraction of times a total of six pinpricks applied to the marked area failed to elicit a nocifensive motor response compared with control responses. No responses out of six pinpricks was defined as 100% maximum possible effect. Complete recovery from the cutaneous analgesia elicited by 0.05% and 0.5 desipramine versus 0.05% and 0.5- ropivacaine occurred in 9.7 +/- 0.2 and 19,3 +/- 0.4 versus 2.2 +/- 0.1 and 16.1 +/- 0.2h, respectively [Mean +/- SE]. Addition of epincphrine increase this duration to 14.1 +/- 0.1 and 21.4 +/- 0.2 versus 3.2 +/- 0.1 and 17.0 +/- 0.3 h, respectively. Complete nociceptive blockade after coinjection of 0.25%, desipramine 0.25% ropivacainc and epinephrine lasted 24 +/- 0.5 h, and complete recovery from this block took 33 +/- 0.5 h. Areas under the percent maximum possible effect [MPE] versus time curve were 1.77 +/- 0.24 and 1.47 +/- 0.5% h for 0.5% desipramine and ropivacaine with epinephrine, respectively, and this value was 2.83 +/- 0.62 h. for the coinjected 0.25% desipramine, 0.25 ropivacaine, and epinephrine admixture. Desipramine is a longer-acting local anesthetic [LA] compared with ropivacaine for cutaneous infiltration. Its analgesic effectiveness is significantly enhanced by epinephrine. Coinjection of desipramine and ropivacaine with epinephrine enhances the analgesic duration of both drugs

Effect of chemosensitizers on minimum inhibitory concentrations of fluconazole in candida albicans

To evaluate the effect of chemosensitizers on the in vitro activity of fluconazole against Candida albicans strains. Using Clinical Laboratory Standard Institute method, antifungal activity of fluconazole was determined alone and in combination with 16 chemosensitizers that included verapamil, reserpine, quinine, quinidine, gemfibrozil, lansoprazole, tamoxifen, diltiazem, desipramine, nicardipine, cyclosporine, chlorpromazine, prochlorperazine, promethazine, thioridazine, and trifluoperazine. Further studies were done using double combinations of selected chemosensitizers with fluconazole [28 combinations]. For testing combinations, half of the minimum inhibitory concentration [MIC] of each agent was selected in order to avoid the effect of the drug alone. One reference strain [ATCC90028] and one clinical isolate of C. albicans were used for testing the in vitro activity. Broth dilution method was used to determine the MICs of fluconazole and chemosensitizers. Of the 16 chemosensitizers tested, 3 exhibited in vitro activity by increasing fluconazole susceptibility to 7-fold. The MICs of the reference strain and clinical isolate for fluconazole were 5.5 and 0.55 MU g/ml, respectively, and these were reduced to 0.76 MU g/ml by gemfibrozil, 0.83 MU g/ml by quinine, and 0.76 MU g/ml by chlorpromazine in the reference strain, with MIC reduction to 0.08 MU g/ml by all three chemosensitizers in the clinical isolate. Some double combinations reduced the MIC of fluconazole to 10- to 100-fold, even when the chemosensitizers were not effective alone. The most effective double combinations were those of chlorpromazine with either reserpine or nicardipine

Estudio multivariado del test de bebida en campo abierto con ratas hiponutridas y desipramina com droga antipánico / Open field drink test-multivaried study with undernourished rats and desipramine as an antipanic drug

Los modelos animales de aproximación-evitación son útiles para el estudio inicial de drogas con efecto sobre la ansiedad pero los componentes de la ansiedad valorados por estos modelos continúan pobremente definidos. Los modelos complejos de evaluación permiten inferencias más completas que aquellos que evalúan sólo una conducta. Estudios previos demuestran que el antidepresivo tricíclico desipramina ejerce un selectivo efecto anticonflicto sobre ratas adultas sometidas a un programa de privación proteica en edad perinatal, en parámetros de conducta espontánea (laberinto en cruz elevado) e ingesta condicionada (Geller-Seifter). Dichas ratas hiponutridas muestran alteraciones en la neurotransmisión noradrenérgica que se asemejan a la activación generalizada del sistema noradrenérgico que presentan los pacientes que sufren ataques de pánico. Se evaluó la actividad anticonflicto de la desipramina en una prueba de conflicto etológico: el test de bebida en campo abierto, sin descartar a priori ninguna conducta, bajo un enfoque multivariado. Este enfoque no ha sido considerado en estudios previos de campo abierto y drogas antipánico. Sobre cuatro variables seleccionadas por análisis factorial, la administración de desipramina a una dosis de 10mg/kg por sólo 7 días produjo una significativa interacción dieta × droga, consistente con estudios previos. La interacción fue independiente de los efectos de ambos tratamientos sobre el peso o la ingesta y se expresó, en las ratas hiponutridas, como un decremento en todas las conductas excepto en el tiempo de bebida con respecto a las ratas controles que mostraron, en general, un decremento en todas las conductas excepto en la frecuencia de acicalamiento.

Do desipramine and fluoxetine ameliorate the extent of colonic damage induced by acetic acid in rats?

The present study was aimed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs; desipramine and fluoxetine, administered in two different doses, on experimentally induced colitis in rats. Two doses for each drug [10, 20 mg/kg/d] were injected intraperitoneally in forty eight adult male albino rats for 2 weeks after induction of colitis by intra-colonic administration of 2ml 3% acetic acid. Several parameters including, macroscopic [ulcer score index], microscopic [histological] and biochemical such as myeloperoxidase [MPO], reduced glutathione [GSH], tumor necrosis factor alpha [TNF-alpha] and interleukin-1 Beta [IL-1beta] were measured using standard assay procedures. The study demonstrated that both desipramine and fluoxetine significantly attenuated the extent and the severity of the macroscopic and microscopic histological signs of cell damage. Both drugs significantly reduced tissue MPO activity in a dose dependent manner. Both desipramine and fluoxetine at either dose increased significantly the GSH in colonic tissue. On the contrary, both desipramine and fluoxetine significantly reduced TNF-alpha and IL-beta in a dose dependent manner. However, desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF-alpha compared to the effect of the smaller dose, and on the contrary, fluoxetine at the dose of 10 mg/kg showed more decrease in the level of IL-beta compared to the effect of the larger dose. The available data indicate that both desipramine and fluoxetine have anti-inflammatory and antioxidants effects in experimentally induced colitis in rats opening the avenue to their possible protective role in patients with inflammatory bowel disease

Amitriptyline, Desipramine, and Paroxetine Inhibit Nitric Oxide Production in Primary Schwann Cell Cultures of Rats / 대한마취과학회지

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.

Padronização de método utilizando a cromatografia a gás para determinação quantitativa de imipramina e desipramina em amostras de soro para fins de monitorização terapêutica / Standardization of method using gas chromatography for the quantification of imipramine and desipramine in sample of serum for therapeutic drug monitoring

Antidepressivos tricíclicos são eficazes e de custo acessível e, não obstante seus efeitos colaterais, são ainda usados no tratamento da depressão. Devido ao fato de apresentarem variações consideráveis de cinética e faixa terapêutica estreita, a monitorização terapêutica se faz necessária, para evitar efeitos sub-terapêuticos ou tóxicos. Neste trabalho foi desenvolvido um método para quantificação de imipramina e desipramina em amostras de soro utilizando a cromatografia gasosa com coluna capilar e detetor de nitrogênio e fósforo com finalidade de monitorização terapêutica. Nas condições padronizadas imipramina, desipramina e padrão interno (clomipramina) eluiram com tempos de retenção de...

Diseño tecnológico de tabletas de Desipramina de liberación controlada / Technological design of controlled-release desipramine tablets

Se realizó un estudio preliminar con la finalidad de obtener tabletas de clorhidrato de desipramina (75 mg) de liberación controlada de lo cual no existen antecedentes de elaboración en la literatura universal. Se diseñaron 5 variantes tecnológicas de formulación, y se obtuvieron resultados muy alentadores al emplear como agentes retardantes dextrana técnica cubana e hidroxipropilmetilcelulosa (HPMC) en la masa y aglutinarla con una solución clorofórmica de alcohol cetílico, con lo cual se obtienen tabletas con excelentes propiedades físico--mecánicas y tecnológicas, y una satisfactoria cinética de disolución con un t100 porciento de aproximadamente 14 h de ensayo in vitro

Effects of Various Tricyclic Antidepressants on Contractile Response of the Rat Vas Deferens to Electrical Stimulation of Hypogastric Nerve / 대한비뇨기과학회지

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.

Antidepressivos / Antidepressants

Os medicamentos antidepressivos tornaram a depressäo um problema médico com elevado potencial tratavel. Nas últimas décadas houve um grande avanço na pesquisa e novos compostos surgiram. Os antidepressivos de primeira geraçäo tiveram seu uso limitado devido a tolerabilidade e toxicidade. Os novos compostos, embora mais seguros, näo se mostraram superiores aos antidepressivos tradicionais. Neste artigo o autor revisa a farmacologia e as indicaçöes dos antidepressivos, assim como as indicaçöes e a eficácia diferencial entre os compostos clássicos e de nova geraçäo(au)

An Autoradiographic Study on the Rat Neostriatal Dopamine Receptor Changes after 6-hydroxydopamine Injection into the Medial Prefrontal Cortex / 신경정신의학

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.

Intracisternal antidepressants suppressed the nociceptive jaw opening reflex in freely moving rats

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 musec duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of 15 microgram imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to 76+/-6% of the control. Intracisternal administration of 30 jig desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to 48 +/- 2, 27 +/- 8, or 25 +/- 5% of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from 23+/-2 to 69+/-4%, from 32+/-5 to 80+/-9%, and from 24+/-6 to 77+/-5% of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

Chronic Antidepressant Administration Increases the Expression of PhosphoCREB(Phosphorylated Cyclic AMP Response Element Binding Protein) in Rat Hippocampus / 신경정신의학

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.

DEVELOPMENT OF A PAIN ASSESSMENTMODEL ANDEFFETS OF ANTIDEPRESSANTS ON NOCICEPTIVEJAWOPENING REFLEX IN FREE MOVING RATS

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.

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.

Psicoterapia cognitiva e comportamental do transtorno do pânico e da agorafobia como uma alternativa eficaz e crítica aos tratamentos biológicos / Cognitive and behavorial psychotherapy of panic disorder and agoraphobia as an effective and critical therapeutic alternative to biological approaches to treatment

Modelos etiólogicos e estratégias de tratamento cognitivas e comportamentais para o transtorno do pânico e da agarafobia são revistos. Uma discussão dos problemas epidemiológicos e clínicos associados a uma opção por: (1) um enfoque biológico que enfatiza apenas tratamentos farmacológicos; ou por (2) um enfoque psicológico que valoriza apenas tratamentos psicoterapêuticos é realizada, apontando para a necessidade de uma definição mais precisa da natureza destes transtornos e de seus tratamentos, tendo em vista as implicações de longo prazo, quando se busca uma remissão pura e simples da ansiedade. Defende-se a idéia de que a investigação cinetífica em um ou outro nível é igualmente relevante e irredutível; e que a escolha de uma ou outra estratégia de tratamento se dê por fatores específicos do problema de cada paciente mais do que por uma tendenciosidade adquirida profissionalmente

Noradrenergic Changes in an Experimental Model of Parkinsonism Using 6-hydroxydopamine

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.

Dopamine receptor mediated antidepressant action of B-HT 920 in mice.

Possible involvement of dopaminergic (DAergic) system in forced swimming-induced immobility (despair behaviour) was investigated in mice. B-HT 920 (0.05 and 0.1 mg/kg), a post-synaptic DAergic agonist, produced a dose dependent reduction in immobility period, which was sensitive to blockade by haloperidol (0.5 mg/kg) and sulpiride (100 mg/kg). This effect was also blocked by alpha 2 antagonist yohimbine (5 mg/kg). SKF 38393 (5 mg/kg), a D1-DA agonist potentiated the action of B-HT 920. Reserpinization (2 mg/kg, 24 hr prior) produced despair immobility in mice. When a low dose of B-HT 920 (0.05 mg/kg) was given to reserpinized animals, the duration of immobility period was further increased. But on the other hand, a higher dose (0.1 mg/kg) of it reduced reserpine-induced immobility. Desipramine (5 and 10 mg/kg), elicited a dose dependent reduction in the immobility period, which was sensitive to blockade by sulpiride (100 mg/kg). Desipramine (10 mg/kg) showed a diphasic response in combination with B-HT 920, i.e., a potentiation of the response due to a low dose of B-HT 920 (0.05 mg/kg) and an antagonism of the response due to a higher dose of B-HT 920 (0.1 mg/kg), respectively. SKF 38393 (5 mg/kg), potentiated the action of desipramine (5 mg/kg). SKF 38393 (5 mg/kg) further potentiated the action of desipramine (5 mg/kg) and B-HT 920 (0.05 mg/kg). These observations suggests that B-HT 920 reduces behavioural immobility by DAergic mechanism and desipramine also modulates D2-DA receptors in its anti-depressant action.