Effects of SCH23390 and Raclopride on Anxiety-Like Behavior in Rats Tested in the Black-White Box

Timothy, Carryl; Costall, B.; Smythe, James W.

doi:10.1016/s0091-3057(98)00157-9

Cited by 37 publications

(14 citation statements)

References 27 publications

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“…(Increased anxiety is often associated with Parkinson's disease.) Consistent with this possibility, treatment with D2 but not D1 dopamine receptor antagonists increases anxiety in rodents (36). Finally, locomotion of the heterozygous knock-in mice is extremely sensitive to nicotine, suggesting that these mice may also become a model for effects of nicotine on mammalian brain and behavior.…”

Section: Discussionmentioning

confidence: 79%

Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety

Labarca

Schwarz

Deshpande

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

175

170

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Knock-in mice were generated that harbored a leucine-to-serine mutation in the ␣4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.T he mechanism leading from nicotine intake to addiction is not known in detail, but it begins with the activation of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine elicits dopamine release in several regions of the brain, presumably leading to the reward, motor, and addictive effects (1, 2). The highest-affinity and most abundant nicotine binding in the brain corresponds to the ␣4␤2 nAChR (3). The ␣4 subunit is the principal partner for the ␤2 subunit in brain; ␤2-containing receptors play an important role in nicotine self-administration, in nicotine-stimulated electrophysiological responses in midbrain neurons, and in nicotine-stimulated dopamine release in the ventral striatum (4, 5). The ␣4 subunit and tyrosine hydroxylase are colocalized in dopaminergic neurons (6). Epidemiological studies show that smokers have a lower incidence of Parkinson's disease (7,8), suggesting a protective effect of nicotine via modulation of the dopaminergic system. Both ␣4 and ␤2 knockout mice show only subtle alterations in their physiology or behavior until they reach old age (4, 9, 10). We have used a complementary strategy to understand the roles of ␣4-containing nAChRs. We reasoned that gain of function mutations might generate more noticeable phenotypes, and that these phenotypes would gain relevance from the fact that nicotine and some candidate analgesics (11) are agonists. We have generated lines of knock-in mice by introducing a point mutation into the M2 transmembrane region of the ␣4 subunit to produce a hypersensitive receptor. Materials and MethodsXenopus Oocyte Injections and Electrophysiology. The ␣4 and ␤2 subunits were subcloned into pAMV-PA (12). Capped mRNA transcripts were prepared, and ␣4͞␤2 (2 ng, 1:1) or ␣4L9ЈS͞␤2 (0.2-0.5 ng, 1:1) were microinjected into Xenopus oocytes (12). Twenty-four to seventy-two hours later, two-electrode voltage clamp recordings (12) were made in solutions containing zero Ca 2ϩ .Knock-in Mouse Construction. A 129͞SvJ ␣4 genomic clone containing exon 5 and the L9ЈS mutation was inserted into pKO Scrambler V907 (Lexicon-Genetics, The Woodland...

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Section: Discussionmentioning

confidence: 79%

Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety

Labarca

Schwarz

Deshpande

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

175

170

View full text Add to dashboard Cite

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“…Therefore, the criteria for evaluating anxiety are different between the human and the rat. Based on previous studies, the criteria for evaluating anxiety behavior in rats includes the time within the black chamber and white chamber, the number of intercompartmental crosses, and activity in the white chamber and black chamber [42]–[44], [47], [48]. In the present study, we also explored whether transient global ischemia would induce anxiety behavior.…”

Section: Discussionmentioning

confidence: 98%

“…Although the black-white box was widely used to detect anxiety by stress [42]–[45], it has recently been employed to investigate visual function [13]. An animal with light perception will escape from the white chamber to the black chamber.…”

Section: Discussionmentioning

confidence: 99%

Changes in Retinal Morphology, Electroretinogram and Visual Behavior after Transient Global Ischemia in Adult Rats

Zhao

Xiang

et al. 2013

PLoS ONE

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The retina is a light-sensitive tissue of the central nervous system that is vulnerable to ischemia. The pathological mechanism underlying retinal ischemic injury is not fully understood. The purpose of this study was to investigate structural and functional changes of different types of rat retinal neurons and visual behavior following transient global ischemia. Retinal ischemia was induced using a 4-vessel occlusion model. Compared with the normal group, the number of βIII-tubulin positive retinal ganglion cells and calretinin positive amacrine cells were reduced from 6 h to 48 h following ischemia. The number of recoverin positive cone bipolar cells transiently decreased at 6 h and 12 h after ischemia. However, the fluorescence intensity of rhodopsin positive rod cells and fluorescent peanut agglutinin positive cone cells did not change after reperfusion. An electroretinogram recording showed that the a-wave, b-wave, oscillatory potentials and the photopic negative response were completely lost during ischemia. The amplitudes of the a- and b-waves were partially recovered at 1 h after ischemia, and returned to the control level at 48 h after reperfusion. However, the amplitudes of oscillatory potentials and the photopic negative response were still reduced at 48 h following reperfusion. Visual behavior detection showed there was no significant change in the time spent in the dark chamber between the control and 48 h group, but the distance moved, mean velocity in the black and white chambers and intercompartmental crosses were reduced at 48 h after ischemia. These results indicate that transient global ischemia induces dysfunction of retinal ganglion cells and amacrine cells at molecular and ERG levels. However, transient global ischemia in a 17 minute duration does not appear to affect photoreceptors.

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“…An increase in dopaminergic transmission has been demonstrated to aggravate anxiety [34], and the D 1 receptor antagonist SCH23390 exhibits clear anxiolytic-like effects [33, 35, 36]. However, D 2 receptor ligands can produce either anxiogenic [33, 37] or anxiolytic-like effects in animal models [28, 38, 39]. D 1 dopamine receptors are mainly found at postsynaptic sites, whereas D 2 dopamine receptors are localized both presynaptically (where they act as autoreceptors) and postsynaptically.…”

Section: Discussionmentioning

confidence: 99%

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor

Mi¹,

Liu²,

Zhang

et al. 2017

PLoS ONE

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Tetrahydroprotoberberines (THPBs) are isoquinoline alkaloids isolated from the Chinese herb Corydalis yanhusuo. In the present study, we performed competitive binding assays to examine the binding of l-THBr to neurotransmitter receptors known to be involved in sedation, hypnosis and anxiety. Our results show that l-THBr does not interact with GABAergic receptors but has binding affinities for dopamine and serotonin receptors. In addition, cAMP and [35S]GTPγS assays were used to determine the agonist or antagonist properties of l-THBr at dopamine (D1, D2) or serotonin (5-HT) receptors. Our results show that l-THBr displays D1 and D2 antagonist and 5-HT1A agonist properties. Moreover, l-THBr-treated rodents exhibit anxiolytic-like effects in the light/dark box and elevated plus-maze tests, and the anxiolytic effect of l-THBr can be reduced by WAY-100635, a selective 5-HT1A receptor antagonist. Our results suggest that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors.

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Effects of SCH23390 and Raclopride on Anxiety-Like Behavior in Rats Tested in the Black-White Box

Cited by 37 publications

References 27 publications

Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety

Point mutant mice with hypersensitive α4 nicotinic receptors show dopaminergic deficits and increased anxiety

Changes in Retinal Morphology, Electroretinogram and Visual Behavior after Transient Global Ischemia in Adult Rats

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor

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