Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. However, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD.

Use of the overexpectation effect to reduce conditioned seeking behavior controlled by nicotine.

Nicotine produces robust stimulus effects that can be conditioned to form associations with reinforcing nondrug stimuli. We examine how established associations to the nicotine stimulus may be weakened via the overexpectation effect. In two experiments, we separately conditioned sucrose associations to the interoceptive nicotine stimulus (0.

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes.

Varenicline (Chantix) is an FDA-approved smoking cessation aid that is pharmacologically similar to nicotine, the primary addictive component found within tobacco. In support of this similarity, previous drug discrimination research in rats has reported that the internal or interoceptive stimulus effects of nicotine and varenicline share stimulus elements. Those shared elements appear to be mediated, in part, by overlapping action at alpha4beta2-containing nicotinic acetylcholine receptors (nAChRs).

A randomized trial of medical cannabis in patients with stage IV cancers to assess feasibility, dose requirements, impact on pain and opioid use, safety, and overall patient satisfaction.

Purpose: The prevalence of medical cannabis (MC) use in patients with cancer is growing, but questions about safety, efficacy, and dosing remain. Conducting randomized, controlled trials (RCTs) using state-sponsored MC programs is novel and could provide data needed to guide patients and providers.

Methods: A pilot RCT of patients with stage IV cancer requiring opioids was conducted.

Elucidating Electron Storage and Distribution within the Pentaheme Scaffold of Cytochrome Nitrite Reductase (NrfA).

Cytochrome nitrite reductases (CNIR or NrfA) play important roles in the global nitrogen cycle by conserving the usable nitrogen in the soil. Here, the electron storage and distribution properties within the pentaheme scaffold of NrfA were investigated via electron paramagnetic resonance (EPR) spectroscopy coupled with chemical titration experiments. Initially, a chemical reduction method was established to sequentially add electrons to the fully oxidized protein, 1 equiv at a time.

Ca3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons.

Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, Ca3.

Negative allosteric modulation of GABAA receptors inhibits facilitation of brain stimulation reward by drugs of abuse in C57BL6/J mice.

Rationale: There is an emerging body of evidence that implicates a crucial role of γ-aminobutyric acid subtype A (GABAA) receptors in modulating the rewarding effects of a number of abused drugs. Modulation of GABAA receptors may therefore represent a novel drug-class independent mechanism for the development of abuse treatment pharmacotherapeutics.

Objectives: We tested the hypothesis that the GABAA receptor benzodiazepine-site (BDZ) negative modulator Ro15-4513 would reduce the reward-related effects of three pharmacologically dissimilar drugs; toluene vapor, d-methamphetamine, and diazepam using intracranial self-stimulation (ICSS) in mice.

The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain.

The aim of the present study was to determine the impact of α5 nicotinic acetylcholine receptor (nAChR) subunit deletion in the mouse on the development and intensity of nociceptive behavior in various chronic pain models. The role of α5-containing nAChRs was explored in mouse models of chronic pain, including peripheral neuropathy (chronic constriction nerve injury, CCI), tonic inflammatory pain (the formalin test) and short and long-term inflammatory pain (complete Freund's adjuvant, CFA and carrageenan tests) in α5 knock-out (KO) and wild-type (WT) mice. The results showed that paw-licking time was decreased in the formalin test, and the hyperalgesic and allodynic responses to carrageenan and CFA injections were also reduced.

Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation.

Rationale: Despite widespread abuse, there are few validated methods to study the rewarding effects of inhalants. One model that may have utility for this purpose is intracranial self-stimulation (ICSS).

Objectives: This study aims to compare and contrast the ICSS reward-facilitating effects of abused inhalants to other classes of abused drugs.

Conditioned response evoked by nicotine conditioned stimulus preferentially induces c-Fos expression in medial regions of caudate-putamen.

Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS).