HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Behavioral Effects in Female Transgenic Mice

Presenter: Salahuddin Mohammedhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1005/thumbnail.jp

R04. HIV-1 Glycoprotein 120 Promotes Affective Dysfunction in Mice and Medium Spiny Neuron Necrosis

Corresponding author (BioMolecular Sciences): Emaya Moss, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1003/thumbnail.jp

Hiv-1 tat and morphine differentially disrupt pyramidal cell structure and function and spatial learning in hippocampal area ca1: Continuous versus interrupted morphine exposure

About half the people infected with human immunodeficiency virus (HIV) have neurocognitive deficits that often include memory impairment and hippocampal deficits, which can be exacerbated by opioid abuse. To explore the effects of opioids and HIV on hippocampal CA1 pyramidal neuron structure and function, we induced HIV-1 transactivator of transcription (Tat) expression in transgenic mice for 14 d and co-administered time-release morphine or vehicle subcutaneous implants during the final 5 d (days 9–14) to establish steady-state morphine levels. Morphine was withheld from some ex vivo slices during recordings to begin to assess the initial pharmacokinetic consequences of opioid withdrawal. Tat expression reduced hippocampal CA1 pyramidal neuronal excitability at lower stimulating currents. Pyramidal cell firing rates were unaffected by continuous morphine exposure. Behaviorally, exposure to Tat or high dosages of morphine impaired spatial memory. Exposure to Tat and steady-state levels of morphine appeared to have largely independent effects on pyramidal neuron structure and function, a response that is distinct from other vulnerable brain regions such as the striatum. By contrast, acutely withholding morphine (from morphine-tolerant ex vivo slices) revealed unique and selective neuroadaptive shifts in CA1 pyramidal neuronal excitability and dendritic plasticity, including some interactions with Tat. Collectively, the results show that opioid-HIV interactions in hippocampal area CA1 are more nuanced than previously assumed, and appear to vary depending on the outcome assessed and on the pharmacokinetics of morphine exposure

HIV-1 Tat Dysregulates the Hypothalamic-Pituitary-Adrenal Stress Axis and Potentiates Oxycodone-mediated Psychomotor and Anxiety-like Behavior of Male Mice

Graduate students: Salahuddin Mohammed, Department of BioMolecular Sciences, School of Pharmacy; Fakhri Mahdi, Department of BioMolecular Sciences, School of Pharmacy; Alaa N. Qrareya, Department of BioMolecular Sciences, School of PharmacyMajor/Minor: Major: Pharmaceutical Science, School of PharmacyFaculty advisor: Jason J. Paris, Department of BioMolecular Sciences,Research Institute of Pharmaceutical Science, School of Pharmacyhttps://egrove.olemiss.edu/neuro_showcase/1006/thumbnail.jp

Developmental exposure to minor cannabinoids causes morphological and behavioral adverse outcomes in zebrafish larvae

Objectives: Determine if minor cannabinoid exposure results in adverse morphological and behavioral effects in developing zebrafish as was previously measured following THC and CBD exposures; Understand relative potency of the different cannabinoids for developmental toxicities.https://egrove.olemiss.edu/hon_posters/1007/thumbnail.jp

Central Actions of 3α,5α-THP Involving NMDA and GABA\u3csub\u3eA\u3c/sub\u3e Receptors Regulate Affective and Sexual Behavior of Female Rats

© Copyright © 2020 Frye, Qrareya, Llaneza and Paris. The neurosteroid, 5α-pregnan-3α-ol-20-one (known as “allopregnanolone” or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate (NMDA) and GABAA receptors to facilitate rodent sexual behavior. Progestogens can also have anti-anxiety effects, but whether these involve actions of centrally-derived 3α,5α-THP or these receptors to support reproductively-relevant behavior is not well understood. We investigated the extent to which 3α,5α-THP’s actions via NMDA and/or GABAA receptors in the midbrain VTA influence reproductive behaviors. Estradiol-primed, ovariectomized/adrenalectomized (OVX/ADX) rats received midbrain VTA infusions of vehicle, an NMDA receptor blocker (MK-801; 200 ng), or a GABAA receptor blocker (bicuculline; 100 ng) followed by a second infusion of vehicle or 3α,5α-THP (100 ng). Reproductively-relevant behaviors were assessed: sexual (paced mating), anxiety-like (elevated plus maze), and social (partner preference, social interaction) behavior. Compared to vehicle, intra-VTA infusions of MK-801 exerted anxiolytic-like effects on elevated plus maze behavior and enhanced lordosis. Unlike prior observations in gonadally-intact rats, intra-VTA bicuculline had no effect on the behavior of OVX/ADX rats (likely due to a floor effect). Subsequent infusions of 3α,5α-THP reversed effects on lordosis and infusions of bicuculline inhibited 3α,5α-THP-facilitated lordosis. Thus, NMDA and GABAA receptors may act as mediators for reproductive behavioral effects of 3α,5α-THP in the midbrain VTA

Brain Levels of Prostaglandins, Endocannabinoids, and Related Lipids Are Affected by Mating Strategies

Background. Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. Likewise, prostaglandins (PGs) drive sexual differentiation and initiation of ovulation. Here, we use lipidomics strategies to test the hypotheses that mating immediately activates the biosynthesis and/or metabolism of eCBs and PGs and that specific mating strategies differentially regulate these lipids in the brain. Methods. Lipid extractions and tandem mass spectrometric analysis were performed on brains from proestrous rats that had experienced one of two mating strategies (paced or standard mating) and two nonmated groups (chamber exposed and home cage controls). Levels of PGs (PGE2 and PGF2alpha), eCBs (AEA and 2-AG, N-arachidonoyl glycine), and 4 related lipids (4 N-acylethanolamides) were measured in olfactory bulb, hypothalamus, hippocampus, thalamus, striatum, midbrain, cerebellum, and brainstem. Results. Overall, levels of these lipids were significantly lower among paced compared to standard mated rats with the most dramatic decreases observed in brainstem, hippocampus, midbrain, and striatum. However, chamber exposed rats had significantly higher levels of these lipids compared to home cage controls and paced mated wherein the hippocampus showed the largest increases. Conclusions. These data demonstrate that mating strategies and exposure to mating arenas influence lipid signaling in the brain

R02. HIV-1 Tat Promotes Age-Related Anxiety-like, Antinociceptive, and Neuromuscular Impairments in Aged Male Mice

Corresponding author (BioMolecular Sciences): Alaa Qrareya, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1001/thumbnail.jp

R03. HIV Tat protein activates plasma kallikrein-kinin system in the doxycycline-inducible astrocyte specific HIV-1 Tat transgenic mice

Corresponding author (BioMolecular Sciences): Logan Sneed, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1002/thumbnail.jp

Therapeutic Frameworks in Integration Sessions in Substance-Assisted Psychotherapy: A Systematized Review

Serotonergic psychedelics and related substances have been explored as potential adjuncts in substance-assisted psychotherapy (SAPT) for treating various disorders. SAPT can be divided into three phases: preparation, administration, and integration. Integration is commonly defined as the comprehension and effective application of insights from psychedelic experiences into everyday life. However, there is limited research regarding the most appropriate therapeutic approach during integration sessions in SAPT. In this article, we discuss the current evidence for different therapeutic frameworks for integrations sessions when serotonergic psychedelics and entactogens are used as adjuncts to psychotherapy. We conducted a systematized review of the literature following PRISMA guidelines and searched PsycINFO, MEDLINE, and Cochrane Library databases. The final synthesis included 75 clinical trials, mixed-methods investigations, treatment manuals, study protocols, quasi-experiments, qualitative investigations, descriptive studies, opinion papers, reviews, books and book chapters, published until November 11, 2022. The effects that various therapeutic approaches for integration sessions have on therapeutic outcome have not been investigated by means of rigorous research. Most of the available evidence we retrieved was not supported by empirical data, thus limiting any conclusive statements regarding appropriate therapeutic frameworks for integration sessions for SAPT. Current clinical studies have used a range of therapeutic frameworks with the majority drawing from the humanistic-experiential tradition. While integration is regarded as crucial for the safe application of SAPTHowever, there is currently an insufficient evidence base to suggest that any type of therapy is most effective for guiding integration sessions. Systematic investigation of different therapeutic frameworks for integration and additional therapy-related factors is needed