Publications by authors named "Jasmine A Robinson"

4 Publications

  • Page 1 of 1

Importance of dopaminergic neurotransmission for the RU 24969-induced locomotor activity of male and female rats during the preweanling period.

Naunyn Schmiedebergs Arch Pharmacol 2021 05 18;394(5):903-913. Epub 2020 Nov 18.

Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA.

There is disagreement about whether the locomotor activity produced by serotonin (5-HT) receptor agonists is ultimately mediated through a dopaminergic mechanism or is independent of dopamine (DA) system functioning. Using a developing rat model, we examined whether DA neurotransmission is necessary for the locomotor activity produced by 5-HT receptor stimulation. Depending on experiment, male and female preweanling rats were pretreated with vehicle, the monoamine-depleting agent reserpine, the 5-HT synthesis inhibitor 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), the DA synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), or the D1 and D2 receptor antagonists SCH 23390 and raclopride, respectively. After completing the pretreatment regimen, the behavioral effects of saline and the 5-HT receptor agonist RU 24969 were assessed during a 2-h test session. Locomotor activity in the center and margin of the testing chamber was recorded. RU 24969's locomotor activating effects were sensitive to blockade of the D2 receptor, but not the D1 receptor. The DA synthesis inhibitor (AMPT) significantly attenuated the RU 24969-induced locomotor activity of preweanling rats, as did the 5-HT synthesis inhibitor PCPA. The latter result suggests that presynaptic 5-HT receptors may have a role in mediating RU 24969-induced locomotion during the preweanling period. DA neurotransmission, especially involving D2 receptors, is necessary for the 5-HT-mediated locomotor activity of preweanling rats. The actions of PCPA, reserpine, and SCH 23390 differ substantially between preweanling and adult rats, suggesting that the neural mechanisms underlying these DA/5-HT interactions vary across ontogeny.
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http://dx.doi.org/10.1007/s00210-020-02011-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106618PMC
May 2021

Serotonin 5-HT and 5-HT receptors co-mediate the RU 24969-induced locomotor activity of male and female preweanling rats.

Pharmacol Biochem Behav 2020 02 17;189:172857. Epub 2020 Jan 17.

Department of Psychology, 5500 University Parkway, California State University, San Bernardino, CA 92407, USA.

The serotonin (5-HT) agonist RU 24969 robustly increases the locomotor activity of adult male rats and mice; however, studies using selective antagonists alternately report that 5-HT, 5-HT, or both receptor types mediate RU 24969's locomotor activating effects. The purpose of the present study was to extend these past findings by administering a selective 5-HT agonist and/or antagonists to male and female preweanling rats. This age group was tested because younger rats often exhibit psychopharmacological responses that are quantitatively or qualitatively different from adult rats. In a series of experiments, male and female preweanling rats were pretreated with vehicle, the 5-HT antagonist WAY 100635 (0.5, 1, 5, or 10 mg/kg), or the 5-HT antagonists NAS-181 (5 or 10 mg/kg) or SB 216641 (5 or 10 mg/kg) 30 min before assessment of locomotor activity. Rats were injected with saline or RU 24969 immediately prior to testing. Results showed that RU 24969 (0.625, 1.25, 2.5, or 5 mg/kg) significantly increased the locomotor activity of both male and female preweanling rats (no sex differences were apparent). Antagonism of either the 5-HT or the 5-HT receptor was sufficient to significantly reduce the locomotor activity of RU 24969-treated preweanling rats. Unexpectedly, NAS-181 did not act as a silent receptor antagonist, as both doses of NAS-181 significantly increased the locomotor activity of saline-treated preweanling rats. In sum, the present results show that both the 5-HT and 5-HT receptor systems mediate locomotion during the late preweanling period, and this mediation does not vary according to sex.
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http://dx.doi.org/10.1016/j.pbb.2020.172857DOI Listing
February 2020

Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander disease severity.

Elife 2019 11 4;8. Epub 2019 Nov 4.

Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, United States.

Alexander disease (AxD) is a fatal neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP), which supports the structural integrity of astrocytes. Over 70 GFAP missense mutations cause AxD, but the mechanism linking different mutations to disease-relevant phenotypes remains unknown. We used AxD patient brain tissue and induced pluripotent stem cell (iPSC)-derived astrocytes to investigate the hypothesis that AxD-causing mutations perturb key post-translational modifications (PTMs) on GFAP. Our findings reveal selective phosphorylation of GFAP-Ser13 in patients who died young, independently of the mutation they carried. AxD iPSC-astrocytes accumulated pSer13-GFAP in cytoplasmic aggregates within deep nuclear invaginations, resembling the hallmark Rosenthal fibers observed in vivo. Ser13 phosphorylation facilitated GFAP aggregation and was associated with increased GFAP proteolysis by caspase-6. Furthermore, caspase-6 was selectively expressed in young AxD patients, and correlated with the presence of cleaved GFAP. We reveal a novel PTM signature linking different GFAP mutations in infantile AxD.
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http://dx.doi.org/10.7554/eLife.47789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927689PMC
November 2019

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences.

Behav Brain Res 2020 02 23;379:112302. Epub 2019 Oct 23.

Department of Psychology, California State University, San Bernardino, CA, USA.

The pattern of ketamine-induced locomotor activity varies substantially across ontogeny and according to sex. Although ketamine is classified as an NMDA channel blocker, it appears to stimulate the locomotor activity of both male and female rats via a monoaminergic mechanism. To more precisely determine the neural mechanisms underlying ketamine's actions, male and female preweanling and adolescent rats were pretreated with vehicle, the dopamine (DA) synthesis inhibitor ∝-methyl--p-tyrosine (AMPT), or the serotonin (5-HT) synthesis inhibitor 4-chloro--phenylalanine methyl ester hydrochloride (PCPA). After completion of the pretreatment regimen, the locomotor activating effects of saline, ketamine, d-amphetamine, and cocaine were assessed during a 2 h test session. In addition, the ability of AMPT and PCPA to reduce dorsal striatal DA and 5-HT content was measured in male and female preweanling, adolescent, and adult rats. Results showed that AMPT and PCPA reduced, but did not fully attenuate, the ketamine-induced locomotor activity of preweanling rats and female adolescent rats. Ketamine (20 and 40 mg/kg) caused a minimal amount of locomotor activity in male adolescent rats, and this effect was not significantly modified by AMPT or PCPA pretreatment. When compared to ketamine, d-amphetamine and cocaine produced different patterns of locomotor activity across ontogeny; moreover, AMPT and PCPA pretreatment affected psychostimulant- and ketamine-induced locomotion differently. When these results are considered together, it appears that both dopaminergic and serotonergic mechanisms mediate the ketamine-induced locomotor activity of preweanling and female adolescent rats. The dichotomous actions of ketamine relative to the psychostimulants in vehicle-, AMPT-, and PCPA-treated rats, suggests that ketamine modulates DA and 5-HT neurotransmission through an indirect mechanism.
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http://dx.doi.org/10.1016/j.bbr.2019.112302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917827PMC
February 2020