The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha(1B)-adrenoceptors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antimalarial effect in vitro and lack of modulating effect of desipramine and imipramine

Based on previous studies in vitro of the modulating effect of desipramine on chloroquine-resistance of Plasmodium falciparum, the effect of desipramine and imipramine on freshly isolated resistant Brazilian strains of the parasite was investigated. Both drugs in therapeutic doses showed an unexpected antimalarial effect in vitro in duplicate tests (IC50=44.26 and 46.53 mu g/L for desipramine, and 83.93 and 41.26 mu g/L for imipramine), but no reversal of resistance when added to cultures together with chloroquine.

Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Involvement of alpha(1B)-adrenoceptors in the anti-immobility effect of imipramine in the tail suspension test

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Social separation and diazepam withdrawal increase anxiety in the elevated plus-maze and serotonin turnover in the median raphe and hippocampus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antipanic procedures reduce the strychnine-facilitated wild running of rats

Wild running (WR) behavior of rats seen in response to intense acoustic stimulation of audiogenic seizure-paradigm is very similar to the panic flight and can be facilitated by subconvulsive doses of strychnine. The present work aimed to test whether antipanic procedures, such as dorsal periaqueductal gray (dPAG) lesion and imipramine treatments, affect the strychnine-facilitated WR. In study 1, six Wistar male adult rats with electrolytic lesion of dPAG had their WR completely blocked, whereas it was facilitated in 50% of sham-lesioned control rats by a dose of 0.5 mg/kg of strychnine administered intraperitoneal. This effect was not reproduced with a higher strychnine dose (1.0 mg/kg). In study 2, the effects of imipramine were investigated by testing 36 rats under a dose of strychnine that induces WR in 50% of subjects. They were assigned into three experimental groups: imipramine treatments of 5.0 and 10.0 mg/kg, and infusions of saline. All these treatments were subchronical with three intraperitoneal injections within 24h. Imipramine (10.0mg/kg) reduced the incidence of WR in comparison to the saline results. It is concluded that strychnine-facilitated WR is reduced by antipanic procedures and, therefore, can be viewed as a manifestation closely related to panic. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Use of the elevated T-maze to study anxiety in mice

We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT2B/2C receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT2B/2C receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species. (C) 2003 Elsevier B.V. All rights reserved.

Ethopharmacological evaluation of the rat exposure test: A prey-predator interaction test

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT1A/5-HT2 receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs. © 2012 Elsevier B.V.

Ethopharmacological analysis of the open elevated plus-maze in mice

Exposure of rodents to an open elevated plus-maze (oEPM) elicits antinociception and increases plasma corticosterone levels. However, no studies have yet assessed the defensive behaviour repertoire of animals in this modified test. In Experiment 1, factor analysis was employed to characterise the behavioural profile of mice exposed to the oEPM. Experiments 2 and 3 assessed the effects of acute alprazolam (0.5-1.5. mg/kg; diazepam 0.5-1.5. mg/kg), pentylenetetrazole (10.0-30.0. mg/kg), yohimbine (2.0-6.0. mg/kg), mCPP (0.3-3.0. mg/kg), and acute and chronic fluoxetine (10.0-30.0. mg/kg) and imipramine (1.0-15.0. mg/kg) on behaviours identified in Experiment 1. The factor analyses revealed that behaviour in the oEPM can largely (77% total variance) be accounted for in terms of 3 factors: factor 1 ('. depth exploration'; e.g. head-dipping on the arms), factor 2 ('. cautious exploration of arms'; e.g. flatback approach), and factor 3 ('. risk assessment'; stretched attend postures - SAP). Experiments 2 and 3 showed that, over the dose range used, alprazolam selectively attenuated all measures of defensiveness. Similar, though more modest, effects were seen with diazepam. Confirming the intensity of the emotional response to the oEPM (nociceptive, endocrine and behavioural), relatively few significant behavioural changes were seen in response to the anxiogenic compounds tested. Although acute fluoxetine or imipramine treatment failed to modify behaviour in the oEPM, chronic fluoxetine (but not chronic imipramine) attenuated total flat back approach and increased head dipping outside the central square. Together, the results indicate that the oEPM induces behavioural defensive responses that are sensitive to alprazolam and chronic fluoxetine. © 2013 Elsevier B.V.

Administração subcrônica de nicotina modifica as respostas neuroendócrina e neuroquímica induzidas pelo teste de natação forçada

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigação do envolvimento de subtipos de adrenoceptores α1 no efeito anti-imobilidade da imipramina no teste de suspensão pela cauda

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB