Invega Hafyera (Paliperidone Palmitate): Extended-Release Injectable Suspension for Patients With Schizophrenia.

The objective of this study was to describe the safety, efficacy, and potential role in therapy of once in 6 months paliperidone palmitate formulation (PP6M; Invega Hafyera). PP6M is a long-acting injectable antipsychotic recently approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. A PubMed literature search was conducted using the following terms: paliperidone palmitate and long-acting antipsychotic injections (January 1, 2017, to November 1, 2022).

Extended-Release Viloxazine for the Treatment of Attention-Deficit Hyperactivity Disorder in School-Age Children and Adolescents.

Objective: To describe the efficacy and safety of extended-release viloxazine (viloxazine ER; Qelbree) for the treatment of attention-deficit hyperactivity disorder (ADHD) in school-age children and adolescents (6-17 years).

Data Sources: A literature search was conducted with PubMed using the following terms: viloxazine and ADHD (August 1, 2017 to February 1, 2023).

Study Selection And Data Extraction: All relevant English-language articles examining the efficacy and safety of viloxazine ER were considered for inclusion.

Ponesimod: An Oral Second-Generation Selective Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Multiple Sclerosis.

Objective: To describe the safety, efficacy, and potential role in therapy of ponesimod, which was recently approved by the Food and Drug Administration (FDA) as a therapeutic option for the treatment of multiple sclerosis (MS).

Data Sources: A PubMed literature search using the following terms: ponesimod and MS (January 1, 2012-October 31, 2022). FDA product labeling was also reviewed for pertinent data sources.

Regulator of G-Protein Signaling 5 Protein Deficiency Differentially Influences Blood Pressure, Vascular and Behavioral Effects in Aged Male Mice.

Aging and elevated activity of the renin-angiotensin-system (RAS) are associated with hypertension, vascular and emotional behavioral abnormalities, like anxiety and depression. Many actions of the main effector hormone of the RAS, angiotensin II (Ang II), are mediated by Ang II type 1 receptor whose activity is modulated by the regulator of G-protein signaling 5 (RGS5) protein. We assessed the role of RGS5 on blood pressure, vascular and emotional behavioral outcomes in aged male mice in the presence and absence of chronically elevated Ang II levels.

Pharmacological activation of kappa opioid receptors in the nucleus accumbens core and ventral tegmental area increases the aversive effects of nicotine.

Aversive effects of nicotine play an important role in the development of nicotine dependence. However, neural substrates and/or brain regions that play a role in the aversive effects of nicotine have not been fully identified. Previous work done in our laboratory showed that systemic administration of kappa opioid receptors (KORs) agonist ±U50488 increased the aversive effects of nicotine.

Differential methamphetamine-induced behavioral effects in male and female mice lacking regulator of G Protein signaling 4.

Methamphetamine-induced behavioral effects are mediated by several neurotransmitters that act via the G-protein coupled receptors (GPCRs). The functioning of GPCRs are negatively regulated by regulators of G-protein signaling (RGS) proteins. The goal of this study was to assess the role of two specific RGS proteins namely the RGS2 and the RGS4 proteins in methamphetamine-induced behaviors.

Attenuation of nicotine-induced rewarding and antidepressant-like effects in male and female mice lacking regulator of G-protein signaling 2.

Nicotine-induced rewarding and mood altering effects contribute to the continued use of nicotine and the subsequent development of nicotine dependence. The goal of this study was to assess the role of two specific regulators of G-protein signaling (RGS) proteins namely RGS2 and RGS4 in the above described effects of nicotine. Male and female mice lacking either RGS2 (RGS2 KO) or RGS4 (RGS4 KO), and their respective wildtype (WT) littermates were used in this study.

Prenatal exposure to methamphetamine in rats induces endothelial dysfunction in male but not female adult offspring.

In utero exposure to methamphetamine results in significant developmental, neurological, and behavioral deficits in offspring. However, very little is known about the cardiovascular effects of prenatal methamphetamine exposure in adult offspring. We hypothesized that prenatal methamphetamine exposure causes adverse cardiovascular effects in adult offspring.

Targeting the renin angiotensin system for the treatment of anxiety and depression.

Emotional disorders like anxiety and depression are responsible for considerable morbidity and mortality all over the world. Several antidepressant and anxiolytic medications are available for the treatment of anxiety and depression. However, a significant number of patients either do not respond to these medications or respond inadequately.

Regulator of G-protein signaling 5 protein protects against anxiety- and depression-like behavior.

Anxiety and depression are a major health burden. Angiotensin II, via activation of angiotensin II type 1 receptor (AT1R)-mediated brain oxidative stress and inflammation may contribute to these emotional abnormalities. In this study, we investigated the role of a regulator of G-protein signaling 5 (RGS5) protein, which regulates AT1R activity, in angiotensin II-induced brain oxidative stress, inflammation and anxiety-, and depression-like behavior.

Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits.

Addiction to psychostimulants like cocaine, methamphetamine, and nicotine poses a continuing medical and social challenge both in the United States and all over the world. Despite a desire to quit drug use, return to drug use after a period of abstinence is a common problem among individuals dependent on psychostimulants. Recovery for psychostimulant drug-dependent individuals is particularly challenging because psychostimulant drugs induce significant changes in brain regions associated with cognitive functions leading to cognitive deficits.

Regulator of G protein signaling 2 differentially regulates nicotine-induced anxiolytic- and antidepressant-like effects in mice.

This study assessed the role of regulator of G protein signaling 2 (RGS2) in nicotine-induced anxiolytic- and antidepressant-like effects using RGS2 wildtype (WT) and RGS2 knockout (KO) mice. RGS2 negatively regulates monoaminergic neurotransmission, which is implicated in the pathology of anxiety and depression. We hypothesized that deletion of RGS2 would enhance nicotine-induced anxiolytic- and antidepressant-like effects, which were assessed using the elevated plus maze and tail suspension tests, respectively.

Regulators of G-protein signaling 2 and 4 differentially regulate cocaine-induced rewarding effects.

There is a need to identify new therapeutic targets for the treatment of cocaine addiction due to the rise in cocaine abuse and deaths due to cocaine overdose. Regulator of G protein signaling (RGS) proteins such as RGS2 and RGS4 are widely distributed in brain regions that play a role in drug reward. Importantly, RGS2 and RGS4 negatively regulate G-protein coupled receptor signaling pathways of monoaminergic neurotransmitters that play a role in the rewarding effects of cocaine by enhancing the rate of hydrolysis of Gα-bound guanine nucleotide triphosphate.

Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine.

Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

Background: We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.

Endogenous opioid system: a promising target for future smoking cessation medications.

Background: Nicotine addiction continues to be a health challenge across the world. Despite several approved medications, smokers continue to relapse. Several human and animal studies have evaluated the role of the endogenous opioid system as a potential target for smoking cessation medications.

Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.

Rationale: Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders.

Objectives: Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum.

Attenuation of nicotine-taking and nicotine-seeking behavior by the mGlu2 receptor positive allosteric modulators AZD8418 and AZD8529 in rats.

Rationale: Numerous medication development strategies seek to decrease nicotine consumption and prevent relapse to tobacco smoking by blocking glutamate transmission. Decreasing glutamate release by activating presynaptic inhibitory metabotropic glutamate (mGlu)2/3 receptors inhibits the reinforcing effects of nicotine and blocks cue-induced reinstatement of nicotine-seeking behavior in rats. However, the relative contribution of mGlu2 receptors in nicotine dependence is still unknown.

Neuroscience of nicotine for addiction medicine: novel targets for smoking cessation medications.

Morbidity and mortality associated with tobacco smoking constitutes a significant burden on healthcare budgets all over the world. Therefore, promoting smoking cessation is an important goal of health professionals and policy makers throughout the world. Nicotine is a major psychoactive component in tobacco that is largely responsible for the widespread addiction to tobacco.

Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function.

Glutamatergic transmission in drug reward: implications for drug addiction.

Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society.

Association between nicotine withdrawal and reward responsiveness in humans and rats.

Importance: Reward-related disturbances after withdrawal from nicotine are hypothesized to contribute to relapse to tobacco smoking but mechanisms underlying and linking such processes remain largely unknown.

Objective: To determine whether withdrawal from nicotine affects reward responsiveness (ie, the propensity to modulate behavior as a function of prior reinforcement experience) across species using translational behavioral assessments in humans and rats.

Design, Setting, Participants: Experimental studies used analogous reward responsiveness tasks in both humans and rats to examine whether reward responsiveness varied in (1) an ad libitum smoking condition compared with a 24-hour acute nicotine abstinence condition in 31 human smokers with (n = 17) or without (n = 14) a history of depression; (2) rats 24 hours after withdrawal from chronic nicotine (n = 19) or saline (n = 20); and (3) rats following acute nicotine exposure after withdrawal from either chronic nicotine or saline administration.

Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.

As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors.

Differential role of N-methyl-D-aspartate receptor-mediated glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats.

Nicotine, a major psychoactive component of tobacco smoke, increases glutamate transmission in the nucleus accumbens (NAcc). However, the role of the N-methyl-D-aspartate (NMDA)-mediated glutamatergic neurotransmission in the NAcc shell and core subdivisions in nicotine-dependent behaviors has not been studied. The present study evaluated, in rats, the effects of bilateral administration of the competitive NMDA receptor antagonist LY235959 (0, 0.

Involvement of glutamatergic and GABAergic systems in nicotine dependence: Implications for novel pharmacotherapies for smoking cessation.

Tobacco smoking continues to be a major global health hazard despite significant public awareness of its harmful consequences. Although several treatment options are currently available for smoking cessation, these medications are effective in only a small subset of smokers, and relapse rates continue to be high. Therefore, a better understanding of the neurobiological mechanisms that mediate tobacco dependence is essential for the development of effective smoking cessation medications.