The Elevated Plus-Maze Test: Differential Psychopharmacology of Anxiety-Related Behavior

Pawlak, Cornelius R.; Karrenbauer, B.D.; Schneider, Peggy; Ho, Ying-Jui

doi:10.1177/1754073911421374

Cited by 47 publications

(39 citation statements)

References 163 publications

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“…The elevated plus maze (EPM) has been used for evaluating not only emotionality but also impulsivity in several rodent models of ADHD [16, 32]. Consistent with the findings from the open field test, the Fez1 -KO mice showed increased trends of locomotor activities ( F (5, 44) = 2.818, p = 0.0272; Fig.…”

Section: Resultssupporting

confidence: 71%

Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice

et al. 2017

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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that, while prevalent, has a stagnant track record for advances in treatment. The limited availability of animal models with appropriate face and predictive validities has hampered progress in developing novel neurobiological hypotheses and testing new therapeutic options for this condition. Here, we report that mice deficient in Fez1, a gene specifically expressed in the nervous system with documented functions in neurodevelopment, show hyperactivity and impulsivity phenotypes, which are ameliorated by administering methylphenidate (MPH) or guanfacine (GFC), two pharmacological agents used for ADHD treatment. Fez1-knockout (KO) mice show reduced expression of tyrosine hydroxylase in the midbrain and the brain stem and have reduced levels of dopamine, norepinephrine, or their metabolites in both the nucleus accumbens and the prefrontal cortex. These neurochemical changes in Fez1-KO mice were normalized by MPH or GFC. We propose that Fez1-KO mice can be used as a model to evaluate the role of altered neurodevelopment in the manifestation of ADHD-like behavioral phenotypes, as well as to investigate the neurobiological mechanisms of existing and new pharmacotherapeutic agents for ADHD.

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Section: Resultssupporting

confidence: 71%

Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice

et al. 2017

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“…The EPM has been widely used for assessing anxiety-related behaviors in rodents, as it utilizes the inherent conflict between the rodent’s exploratory nature and their avoidance of potential harm (e.g., elevation and open space; Pawlak et al, 2012). Under this conflict between approach and avoidance, it is suggested that behavioral inhibition mechanisms become active and generate anxiety in normal animals that in turn leads to their limited approach behavior (Gray and McNaughton, 2000; Pawlak et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Timing of amphetamine exposure in relation to puberty onset determines its effects on anhedonia, exploratory behavior, and dopamine D1 receptor expression in young adulthood

Kang

Galvez

et al. 2016

Neuroscience

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Non-medical use of amphetamine (AMPH) among adolescents is prevalent, which is problematic given the potential consequences of developmental drug exposure on brain function and behavior. Previously we found in adult male rats that AMPH exposure starting before puberty induces a persistent decrease in dopamine D1 receptor (D1R) function in the medial prefrontal cortex (mPFC). Here we investigated if this dysfunction was associated with changes in D1R expression in the mPFC and nucleus accumbens (NAc). We also determined if starting drug exposure well before or near the onset of puberty would influence AMPH-induced changes in D1R expression and behavior. Male and female Sprague-Dawley rats were treated once every other day (10 injections total) with saline or 3 mg/kg AMPH (i.p.) from either postnatal day (P) 27 to 45 (pre-puberty groups; pre-P) or P37 to 55 (peri-puberty groups; peri-P). After 1, 7 and 21 days of withdrawal, sucrose preference tests were performed to assess anhedonia. Exploratory behavior was studied in an open-field arena and on an elevated plus maze (EPM). Rats were then sacrificed for western blot analysis of D1R expression. We found that AMPH withdrawal induced decreases in sucrose preference that persisted in rats with peri-P onset treatment. Pre-P onset AMPH exposure led to increased open arm exploration in the EPM test, as well as a decreased D1R level in the mPFC but not NAc. Our results demonstrated that AMPH exposure starting at different developmental stages resulted in distinct neurobehavioral abnormalities, suggesting an important role of exposure timing in drug-induced plasticity.

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“…Thiébot et al (1980) [54], had advised caution by concluding that the anxiolytic effect of benzodiazepines depends exclusively on a selective effect on serotonergic neurotransmission. The predictive validity of the EPM is good with regard to the effectiveness of benzodiazepine/gamma-aminobutyric acidergic drugs, but inconsistent evidence has been shown for various neuropeptides and serotonergic drugs [55], and an inverse activation of the benzodiazepine receptor plays only a minor role, if any, in the effects of harmine on dopamine release and metabolism in the rat striatum [46]. The significant increase in the number of entries into open arms by pregnant female rats established the effect of harmine on benzodiazepine receptors.…”

Section: Discussionmentioning

confidence: 99%

ESTIMATION OF THE ANXIOLYTIC-LIKE EFFECT OF THE Β-Carboline ALKALOID HARMINE ON STRESSED PREGNANT RATS

Benatoui

Bairi

Tahraoui

2017

Int J Pharm Pharm Sci

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Objective: During the last decade, the role of the β-carboline alkaloid harmine has essentially been studied with regard to its anxiolytic effect, as it was done in our laboratory; therefore, this study has been progressed to cover the effect of this alkaloid on pregnant wistar rats. Methods:The molecule was used at doses of 10 mg/kg, 15 mg/kg, pregnant female rats were divided into three groups according to the stage of pregnancy: first, second, and the third week of pregnancy. Each group has been subdivided into seven subgroups: control group, two treated groups with harmine, acute footshock stress at 1,2mA, sub-acute footshock stress at 0,4mA, psychological stress, and the treated group that footshocked after with 1,2mA, all groups were carried out open field test, plus maze test and light/dark box test. Results:Thigmotaxis is reflected by the significant increase in the traveled distance in peripheral area in the open field of the three groups 'weeks' at dose of 10 mg/kg, the enhancement in the number and time of rearing, at both doses, during the second and the last week, the significant increase in the number of entries 'in open arms' in plus-maze during the first and third weeks at 15 mg/kg, and the significant decreased in time spent in the light compartment of the light/dark box at the same dose of all groups 'weeks' were noticed, which confirm the anxiolytic effect of the alkaloid, even in the case of the footschock stressed pregnant rats of all groups 'weeks' that enhancement of number of enties into open arms during the plus maze test. Conclusion:So we can conclude that the anxiolytic effect of harmine not shortening to male rats, but expands to female pregnant wistar rats, and establishes its effect by diminishing time in light compartment of light/dark box and number of entries in open arms of plus maze, in other hand, the increase in the number and the time of rearing reflects the enhancement of exploratory behavior.

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The Elevated Plus-Maze Test: Differential Psychopharmacology of Anxiety-Related Behavior

Cited by 47 publications

References 163 publications

Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in <b><i>Fez1</i></b>-Deficient Mice

Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in <b><i>Fez1</i></b>-Deficient Mice

Timing of amphetamine exposure in relation to puberty onset determines its effects on anhedonia, exploratory behavior, and dopamine D1 receptor expression in young adulthood

ESTIMATION OF THE ANXIOLYTIC-LIKE EFFECT OF THE Β-Carboline ALKALOID HARMINE ON STRESSED PREGNANT RATS

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