Ethopharmacological analysis of rat behavior on the elevated plus-maze

Cruz, Antonio Pedro Mello; Frei, Fernando; Graeff, Frederico Guilherme

doi:10.1016/0091-3057(94)90472-3

Cited by 762 publications

(494 citation statements)

References 23 publications

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“…The 5-min test procedure began when the animal was placed in the centre of the maze, facing a closed arm. The percent of time spent in open arms and the percent of open arm entries were used as measures of anxiety-like behaviour, while the number of entries into the closed arms was used as an indicator of general motor activity (Cruz et al 1994). As previously described by Gehlert et al (2007), alcoholinduced anxiety was measured by treating rats (N=32) IP with 3.0 g/kg of 20% alcohol or vehicle (saline) and 12 h later running the elevated plus-maze (EPM) test.…”

Section: Alcohol-induced Anxietymentioning

confidence: 99%

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

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Rationale A major clinical concern with the use of cannabinoid receptor 1 (CB1) direct agonists is that these compounds increase alcohol drinking and drug abuserelated behaviours. As an alternative approach, CB1-receptor-mediated activity can be facilitated by increasing anandamide levels with the use of hydrolase fatty acid amide hydrolase (FAAH) inhibitors. Objective Using the selective FAAH inhibitor URB597, we investigated whether activation of the endogenous cannabinoid tone increases alcohol abuse liability, as what happens with the CB1 receptor direct agonists.Materials and methods URB597 was tested on alcohol self-administration in Wistar rats and on homecage alcohol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. In Wistar rats, URB597 effects on alcohol-induced anxiety and on stress-, yohimbineand cue-induced reinstatement of alcohol seeking were also evaluated. For comparison, the effect of the CB1 receptor antagonist rimonabant on ethanol self-administration was also tested. Results Under our experimental condition, intraperitoneal (IP) administration of URB597 (0.0, 0.3 and 1.0 mg/kg) neither increased voluntary homecage alcohol drinking in msP rats nor facilitated fixed ratio 1 and progressive ratio alcohol self-administration in nonselected Wistars. In the reinstatement tests, the compound did not have effects on cue-, footshock stress-and yohimbine-induced relapse. Conversely, URB597 completely abolished the anxiogenic response measured during withdrawal after an acute IP administration of alcohol (3.0 g/kg). Rimonabant (0.0, 0.3, 1.0 and 3.0 mg/kg) significantly reduced ethanol self-administration. Conclusions Results demonstrate that activation of the endocannabinoid anandamide system by selective inhibition of FAAH does not increase alcohol abuse risks but does reduce anxiety associated to alcohol withdrawal. We thus can speculate that medication based on the use of endocannabinoid system modulators such as URB597 may offer important advantages compared to treatment with direct CB1 receptor activators.

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Section: Alcohol-induced Anxietymentioning

confidence: 99%

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

et al. 2008

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“…The difference in minimal effective doses between both elevated plus-maze experiments (ie, 0.3 vs 10 mg/kg) is unclear, but can be explained by the use of different species (ie, mouse vs rat), different experimental conditions (ie, stressed vs non-stressed animals) and/or different timing of administration (ie, 60 vs 90 min). The absence of significant alterations in the number of closed arm entries (a reliable measure of locomotor activity; Cruz et al, 1994) in the elevated plusmaze and in the distance traveled in the social interaction test in gerbils indicates that the anxiolytic-like activity was observed at doses that did not impair motor activity. Moreover, it is unlikely that the positive effects of SR58611A in the punished drinking test are due to decreased sensitivity to electric shocks since compounds that are endowed with analgesic properties, such as morphine, are inactive in conflict tests (present results;Griebel et al, 2002b;Vanover et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

Stemmelin

Cohen

Terranova

et al. 2007

Neuropsychopharmacol

109

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The characterization of the first selective orally active and brain-penetrant b 3 -adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stressinduced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the b 3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide.Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the b 3 adrenoceptor suggested that these effects of SR58611A are mediated by b 3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of b 3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.

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“…The apparatus was wiped clean with water and dried after each subject. The primary measures were the percent of total arm time directed towards the open arms (ie, 100 Â open arm/(open arm + closed arm)), a validated index of anxiety-related behavior (Fernandes and File, 1996) and the number of closed arm entries, a specific index of locomotor activity (Cruz et al, 1994 Statistical analysis. To determine the time course of the effects of FG 7142 on total intake, two-way repeatedmeasures (dose and time) ANOVAs were performed on the incremental intake of food and water during 1-h time bins.…”

Section: Microstructural Analysis Of Ingestionmentioning

confidence: 99%

FG 7142 Specifically Reduces Meal Size and the Rate and Regularity of Sustained Feeding in Female Rats: Evidence that Benzodiazepine Inverse Agonists Reduce Food Palatability

Cottone

Sabino

Steardo

et al. 2006

Neuropsychopharmacol

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Benzodiazepine receptor inverse agonists reduce food intake in males, but their actions in females, in whom stress-related eating disorders are more common, as well as their behavioral mode of action remain unclear. The consummatory effects of benzodiazepine receptor ligands have alternately been hypothesized to reflect changes in the hedonic evaluation of food or secondary effects of anxietyrelated or cognitive properties. To test the anorectic mode of action of benzodiazepine inverse agonists, the effects of FG 7142 on feeding microstructure were studied in nondeprived female Wistar rats (n ¼ 32). Microstructure analysis used a novel meal definition that recognizes prandial drinking. On pharmacologically synchronized diestrus I, rats were pretreated (À30 min dark onset) with the benzodiazepine partial inverse agonist FG 7142 (i.p. 0, 3.75, 7.5, 15 mg/kg) in a between-subjects design. FG 7142 delayed the onset of (16-541%), decreased the amount eaten (36-52%) and drunk (63-87%), and reduced the time spent drinking (59-87%) within the first nocturnal meal. Dose-dependent incremental anorexia continued 6 h into the dark cycle, whereas FG 7142 did not suppress the quantity, duration or rate of drinking past the first meal. Treated rats ate smaller meals (17-42%) of normal duration. This reflected that FG 7142 slowed feeding within meals (9-38%) by decreasing the regularity and maintenance of feeding from pellet-to-pellet. FG 7142 did not influence postprandial satiety; meal frequency and inter-meal intervals were unaffected. FG 7142 anorexia was blocked by the benzodiazepine receptor antagonist flumazenil in a 2:1 molar ratio (n ¼ 17 rats). The very early, nonspecific ( + 10 min), but not subsequent (2.5, 4.5 h) feeding-specific phase, of FG 7142 anorexia was mirrored by anxiogenic-like behavior in FG 7142-treated (7.5 mg/ kg) female rats (n ¼ 48) in the elevated plus-maze. Thus, benzodiazepine receptor inverse agonists preferentially lessen the maintenance of feeding in female rats, effects opposite to those of palatable food.

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Ethopharmacological analysis of rat behavior on the elevated plus-maze

Cited by 762 publications

References 23 publications

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Increase of brain endocannabinoid anandamide levels by FAAH inhibition and alcohol abuse behaviours in the rat

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

FG 7142 Specifically Reduces Meal Size and the Rate and Regularity of Sustained Feeding in Female Rats: Evidence that Benzodiazepine Inverse Agonists Reduce Food Palatability

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