Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats

Rusnak, Milan; Květňanský, Richard; Jeloková, Jana; Palkovits, Miklós

doi:10.1016/s0006-8993(01)02126-6

Cited by 73 publications

(52 citation statements)

References 70 publications

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“…This result agreed with previous reports by Rusnak et al (1998Rusnak et al ( , 2001). An ϳ2-fold induction of LC TH mRNA was still observed 24 and 48 h after the last immobilization episode.…”

Section: Downloaded Fromsupporting

confidence: 94%

Chronic Nicotine Treatment Leads to Induction of Tyrosine Hydroxylase in Locus Ceruleus Neurons: The Role of Transcriptional Activation

Sun

Chen²,

Lu³

et al. 2004

Mol Pharmacol

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Chronic nicotine treatment (two daily subcutaneous injections administered ϳ12 h apart for 14 days) is associated with longterm inductions of tyrosine hydroxylase (TH) protein and TH mRNA in locus ceruleus (LC) neurons. These increases persist for at least 3 days after the final nicotine injection in LC cell bodies and for at least 7 to 10 days in LC nerve terminal regions. We tested whether this long-term response is due to sustained stimulation of TH gene transcription rate. A semiquantitative reverse transcription-polymerase chain reaction assay was developed to assess changes in the levels of TH RNA primary transcripts; these changes are an indirect measurement of changes in TH gene transcription rate. TH RNA primary transcript levels increase rapidly in the LC after a single nicotine administration and return to basal levels by 24 h. A similar rapid and transient induction of LC TH RNA primary transcripts occurs after chronic nicotine administration. In contrast, TH RNA primary transcript levels remain elevated for a sustained period of time (at least 1 day) in the adrenal medulla after chronic nicotine administration. Similar rapid, but transient changes in LC TH RNA primary transcript levels are observed after repeated immobilization stress. These results suggest that TH gene transcription rate in the LC is stimulated rapidly after each nicotine injection; however, in contrast to the adrenal medulla, there is no sustained transcriptional response elicited by chronic nicotine treatment or repeated immobilization stress in the LC, suggesting that post-transcriptional mechanisms may also play a role in these long-term responses.

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Section: Downloaded Fromsupporting

confidence: 94%

Chronic Nicotine Treatment Leads to Induction of Tyrosine Hydroxylase in Locus Ceruleus Neurons: The Role of Transcriptional Activation

Sun

Chen²,

Lu³

et al. 2004

Mol Pharmacol

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“…As shown previously (Nú ñ ez et al, 2007b(Nú ñ ez et al, , 2009, high densities of TH-positive cell bodies and fibers were seen at the level of NTS, which corresponds to the acknowledged distribution of TH mRNA (Rusnak et al, 2001). TH neurons were very strongly and ubiquitously stained for CRF1R.…”

Section: Resultssupporting

confidence: 79%

Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal

Navarro‐Zaragoza¹,

Núñez²,

Laorden³

et al. 2010

Mol Pharmacol

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The role of stress in drug addiction is well established. The negative affective states of withdrawal most probably involve recruitment of brain stress neurocircuitry [e.g., induction of hypothalamo-pituitary-adrenocortical (HPA) axis, noradrenergic activity, and corticotropin-releasing factor (CRF) activity]. The present study investigated t$he role of CRF receptor-1 subtype (CRF1R) on the response of brain stress system to morphine withdrawal. The effects of naloxone-precipitated morphine withdrawal on noradrenaline (NA) turnover in the paraventricular nucleus (PVN), HPA axis activity, signs of withdrawal, and c-Fos expression were measured in rats pretreated with vehicle, CP-154526 [N-butyl-N-ethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[3,2-e]pyrimidin-4-amine], or antalarmin (selective CRF1R antagonists). Tyrosine hydroxylase-positive neurons expressing CRF1R were seen at the level of the nucleus tractus solitarius-A 2 cell group in both control and morphine-withdrawn rats. CP-154526 and antalarmin attenuated the increases in body weight loss and irritability that were seen during naloxone-induced morphine withdrawal. Pretreatment with CRF1R antagonists resulted in no significant modification of the increased NA turnover at PVN, plasma corticosterone levels, or c-Fos expression that was seen during naloxone-induced morphine withdrawal. However, blockade of CRF1R significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropin levels. These results suggest that the CRF1R subtype may be involved in the behavioral and somatic signs and in adrenocorticotropin release (partially) during morphine withdrawal. However, CRF1R activation may not contribute to the functional interaction between NA and CRF systems in mediating morphine withdrawalactivation of brain stress neurocircuitry.

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“…It is intriguing that VMAT2 mRNA and tetrabenazine binding are decreased also in limbic areas of the Flinders rat (Schwartz et al, 2003) and this animal shows many of the same endophenotypes as the Vmat2 HET mice. Previous investigations have shown that VMAT2 expression and/or its subcellular distributions are modulated by estrogen, stress, monoamine oxidase inhibitors, lithium, psychostimulants, and bupropion (Rehavi et al, 1998;Rusnák et al, 2001;Zucker et al, 2001Zucker et al, , 2005Riddle et al, 2002;Rau et al, 2005). In contrast, chronic reserpine or paroxetine treatments exert no effects on VMAT2 expression, at least in brain regions that contain 5-HT neurons (Vilpoux et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

Fukui¹,

Rodriguiz²,

Zhou³

et al. 2007

J. Neurosci.

136

144

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The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whether Vmat2 heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times for Vmat2 heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTP␥S binding indicated that ␣ 2 -adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

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Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats

Cited by 73 publications

References 70 publications

Chronic Nicotine Treatment Leads to Induction of Tyrosine Hydroxylase in Locus Ceruleus Neurons: The Role of Transcriptional Activation

Chronic Nicotine Treatment Leads to Induction of Tyrosine Hydroxylase in Locus Ceruleus Neurons: The Role of Transcriptional Activation

Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal

Vmat2Heterozygous Mutant Mice Display a Depressive-Like Phenotype

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