Role of the Dorsomedial Hypothalamus in Mediating the Response to Benzodiazepines on Trial 2 in the Elevated Plus-Maze Test of Anxiety

File, Sandra E.; González, L.; Gallant, Rachael

doi:10.1016/s0893-133x(99)00028-7

Cited by 49 publications

(17 citation statements)

References 46 publications

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“…At the highest dose (10.0 mg/kg), however, the WAY 161503-induced changes in open arm exploration and risk-assessment were accompanied by a robust hypolocomotion as indicated by reduction in the absolute number of closed-arm entries. As a whole these results further corroborate previously reported studies showing selective, preferential and non-selective 5-HT 2C agonists to exhibit anxiogeniclike properties and locomotor impairments (Kennett et al 1989;Rodgers et al 1992;Grewal et al 1997;Mora et al 1997;Olivier et al 1998;Setem et al 1999;Bagdy et Repeated EPM exposures are known to reduce or abolish the anxiolytic-like effects of benzodiazepines, a phenomenon known as "one-trail tolerance" or acute tolerance in this test (File, 1990;File, 1993;File, Zangrossi, Viana, & Graeff, 1993;File, Gonzalez, & Gallant, 1999;Frussa-Filho & Ribeiro, 2002;Vargas, Da Cunha, & Andreatini, 2006;Albrechet-Souza, Borelli, & Brandão, 2008). Our present results with the 5-HT 2C agonist WAY 161503 showed that both the first and second EPM exposures were similarly able to detect anxiogenic-like effects.…”

Section: Discussionsupporting

confidence: 91%

Antidepressant- and anxiogenic-like effects of acute 5-HT2C receptor activation in rats exposed to the forced swim test and elevated plus maze.

Gomes¹,

Greidinger²,

Salviano³

et al. 2010

Psychology & Neuroscience

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This study investigated the behavioral effects in the forced swim test (FST) and the elevated plus-maze (EPM) of acute administration of WAY 161503 ([4aR]-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5[6H]-one), a selective 5-HT 2C receptor agonist with putative antidepressant-like properties. Fifteen minutes after intraperitoneal (i.p.) injections of either WAY 161503 (1, 3 and 10 mg/kg) or saline, naive male Wistar rats were exposed to the EPM for 5 min to assess classical and ethological anxiety-like measures. Immediately after EPM exposure, each animal was exposed to the FST, and the latency to the first episode of immobility was recorded (trial session). Twenty-four hours later, the rats were reexposed to a second EPM-FST exposure sequence (test session for FST) under the effect of the same pharmacological treatment. The two lowest WAY 161503 doses selectively reduced open-arm exploration and increased risk-assessment without affecting locomotor activity. This selective anxiogenic-like effect was observed in both the first and second EPM exposures. The highest WAY 161503 dose produced robust locomotor impairment. In the FST, the same WAY 161503 doses significantly increased the latency to the first immobility in the test session, a behavioral profile that suggests an antidepressant-like action. These results further support the involvement of 5-HT 2C receptors in the mediation of anxiety and suggest an intricate relationship between anxiogenic-and antidepressant-like actions.

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Section: Discussionsupporting

confidence: 91%

Antidepressant- and anxiogenic-like effects of acute 5-HT2C receptor activation in rats exposed to the forced swim test and elevated plus maze.

Gomes¹,

Greidinger²,

Salviano³

et al. 2010

Psychology & Neuroscience

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“…Indeed, in our confirmatory factor analysis study of na CD-1 mouse behaviour in the elevated plus-maze (n=200), open entries, open time ratio, unprotected head dips and unprotected stretch attends were reduced by approximately 50% in trial 2 (Wall and Messier 2000b). In contrast to these between-trial behavioural response differences, indicating some form of learning during trial 1 (Espejo 1997;File et al 1998File et al , 1999File et al , 2000Holmes and Rodgers 1998;Kenny et al 2000;Ouagazzal et al 1999), there were some noticeable increases between the trial 1 (drug injection) and trial 2 (no drug injection) unprotected exploration measures in experiment 1. Whereas the vehicle group showed lower trial 2 unprotected exploration activity levels, the 5-and 20-nmol groups actually showed some higher trial 2 unprotected exploration activity levels (Fig.…”

Section: Discussionmentioning

confidence: 79%

Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice

2001

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(1) Enhanced ACh transmission in the vmPFC induces anxiety in challenging environments and enhances spontaneous working memory performance. (2) Blocking or activating postsynaptic M1 receptors in the vmPFC may truncate or exaggerate, respectively, afferent anxiety-relevant information. (3) IL pirenzepine and McN-A-343 exert long-term opposite effects on aversive learning during trial 1 in the elevated plus-maze.

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“…EPM apparatus consists of two opposite open arms 50 × 10 cm and two opposite arms enclosed by 40 cm high walls and elevated 50 cm from the floor. The arms are connected by a central 10 × 10 cm square, and thus the maze forms a "plus" shape (File et al, 1999).…”

Section: Elevated Plus-maze (Epm)mentioning

confidence: 99%

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Getachew¹,

Hauser²,

Taylor³

et al. 2008

Pharmacology Biochemistry and Behavior

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Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxietylike behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism.

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Role of the Dorsomedial Hypothalamus in Mediating the Response to Benzodiazepines on Trial 2 in the Elevated Plus-Maze Test of Anxiety

Abstract: Trial 2 in the elevated plus-maze provides an animal model of specific phobia (fear of heights). On this trial

Cited by 49 publications

References 46 publications

Antidepressant- and anxiogenic-like effects of acute 5-HT2C receptor activation in rats exposed to the forced swim test and elevated plus maze.

Antidepressant- and anxiogenic-like effects of acute 5-HT2C receptor activation in rats exposed to the forced swim test and elevated plus maze.

Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice

Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

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