Cocaine Self-Administration Influences Central Nervous System Immune Responses in Male HIV-1 Transgenic Rats.

Cocaine use increases the neurotoxic severity of human immunodeficiency virus-1 () infection and the development of HIV-associated neurocognitive disorders (). Among the studied cellular mechanisms promoting neurotoxicity in HIV-1 and cocaine use, central nervous system () immunity, such as neuroimmune signaling and reduced antiviral activity, are risk determinants; however, concrete evidence remains elusive. In the present study, we tested the hypothesis that cocaine self-administration by transgenic HIV-1 () rats promotes CNS inflammation.

Intestinal Barrier Dysfunction in the Absence of Systemic Inflammation Fails to Exacerbate Motor Dysfunction and Brain Pathology in a Mouse Model of Parkinson's Disease.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease associated with aging. PD patients have systemic and neuroinflammation which is hypothesized to contribute to neurodegeneration. Recent studies highlight the importance of the gut-brain axis in PD pathogenesis and suggest that gut-derived inflammation can trigger and/or promote neuroinflammation and neurodegeneration in PD.

Mitochondrial function influences expression of methamphetamine-induced behavioral sensitization.

Repeated methamphetamine use leads to long lasting brain and behavioral changes in humans and laboratory rats. These changes have high energy requirements, implicating a role for mitochondria. We explored whether mitochondrial function underpins behaviors that occur in rats months after stopping methamphetamine self-administration.

Gut and brain profiles that resemble pre-motor and early-stage Parkinson's disease in methamphetamine self-administering rats.

Introduction: Methamphetamine is a potent psychomotor stimulant, and methamphetamine abusers are up to three times more likely to develop Parkinson's disease (PD) later in life. Prodromal PD may involve gut inflammation and the accumulation of toxic proteins that are transported from the enteric nervous system to the central nervous system to mediate, in part, the degeneration of dopaminergic projections. We hypothesized that self-administration of methamphetamine in rats produces a gut and brain profile that mirrors pre-motor and early-stage PD.

The role of dopamine pharmacotherapy and addiction-like behaviors in Parkinson's disease.

Addictions involve a spectrum of behaviors that encompass features of impulsivity and compulsivity, herein referred to as impulsive-compulsive spectrum disorders (ICSDs). The etiology of ICSDs likely involves a complex interplay among neurobiological, psychological and social risk factors. Neurobiological risk factors include the status of the neuroanatomical circuits that govern ICSDs.

Using Modern Neuroscience to Inform Opioid Use and Abuse Liability in Adolescents.

Opioid abuse and overdosing have reached epidemic status in the United States, and this epidemic has profound negative effects on the lives of adolescents and their families. A combination of readily available opioids (including illicit opioids, such as heroin, and overprescribed prescription opioid-based painkillers) and an abuse vulnerability inherent to adolescence drives the problem. The pharmacology of opioids in the context of adolescent brain neurobiology helps explain the enhanced vulnerability to drug abuse experienced by the young.

Pharmacological insights into impulsive-compulsive spectrum disorders associated with dopaminergic therapy.

Impulsive-compulsive spectrum disorders are associated with dopamine agonist therapy in some patients. These untoward outcomes occur with direct-acting, full and partial agonists at D2 dopamine family receptors. The disorders typically emerge during chronic treatment, and exhibit common features that are independent of the neurological or psychiatric pathology for which the initial therapy was indicated.

Region-specific changes in markers of neuroplasticity revealed in HIV-1 transgenic rats by low-dose methamphetamine.

Methamphetamine abuse co-occurring with HIV infection presents neuropathology in brain regions that mediate reward and motivation. A neuronal signaling cascade altered acutely by meth and some HIV-1 proteins is the mitogen-activated protein kinase (MAPK) pathway. It remains unknown if chronic co-exposure to meth and HIV-1 proteins converge on MAPK in vivo.

Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known.

Self-administration of methamphetamine alters gut biomarkers of toxicity.

Methamphetamine (METH) is a highly abused psychostimulant that is associated with an increased risk for developing Parkinson's disease (PD). This enhanced vulnerability likely relates to the toxic effects of METH that overlap with PD pathology, for example, aberrant functioning of α-synuclein and parkin. In PD, peripheral factors are thought to contribute to central nervous system (CNS) degeneration.

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.

Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks.

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease.

Pramipexole and ropinirole are dopamine agonists that are efficacious in treating motor disturbances of neuropathologies, e.g., Parkinson's disease and restless legs syndrome.

Dopaminergic lesions of the dorsolateral striatum in rats increase delay discounting in an impulsive choice task.

Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer.

Cortical consequences of HIV-1 Tat exposure in rats are enhanced by chronic cocaine.

The life span of individuals that are sero-positive for human immunodeficiency virus (HIV) has greatly improved; however, complications involving the central nervous system (CNS) remain a concern. While HIV does not directly infect neurons, the proteins produced by the virus, including HIV transactivator of transcription (Tat), are released from infected glia; these proteins can be neurotoxic. This neurotoxicity is thought to mediate the pathology underlying HIVassociated neurological impairments.

Cellular distribution of AMPA receptor subunits and mGlu5 following acute and repeated administration of morphine or methamphetamine.

Ionotropic AMPA receptors (AMPAR) and metabotropic glutamate group I subtype 5 receptors (mGlu5) mediate neuronal and behavioral effects of abused drugs. mGlu5 stimulation increases expression of striatal-enriched tyrosine phosphatase isoform 61 (STEP61 ) which internalizes AMPARs. We determined the rat brain profile of these proteins using two different classes of abused drugs, opiates, and stimulants.

Sensitization by ventral pallidal DAMGO: lack of cross-sensitization to morphine.

Repeated injections of morphine into the ventral pallidum of laboratory rats results in the development and expression of motor sensitization. Although morphine and [D-Ala, N-MePhe, Gly(ol)]-enkephalin (DAMGO) both activate μ-opioid receptors, their influence on receptor-mediated signaling differs; therefore, we determined if they differentially influenced ventral pallidal-mediated motor sensitization. Repeated intraventral pallidal injections of DAMGO led to the development of motor sensitization and this behavior persisted for at least 18 days.

Enduring cortical alterations after a single in-vivo treatment of HIV-1 Tat.

HIV-1 proteins, including the transactivator of transcription (Tat), are believed to be involved in HIV-associated neurocognitive disorders by disrupting Ca²⁺ homeostasis, which leads to progressive dysregulation, damage, or death of neurons in the brain. We have found previously that bath-applied Tat abnormally increased Ca²⁺ influx through overactivated, voltage-sensitive L-type Ca²⁺ channels in pyramidal neurons within the rat medial prefrontal cortex (mPFC). However, it is unknown whether the Tat-induced Ca²⁺ dysregulation was mediated by increased activity and/or the number of the L-channels.

The atypical antidepressant mirtazapine attenuates expression of morphine-induced place preference and motor sensitization.

Opioid abuse and dependence remains prevalent despite having multiple FDA-approved medications to help maintain abstinence. Mirtazapine is an atypical antidepressant receiving attention for substance abuse pharmacotherapy, and its action includes alterations in monoaminergic transmission. As monoamines are indirectly altered by opioids, the current investigation assessed the ability of mirtazapine to ameliorate morphine-induced behaviors.