Addiction Treatment Novel Approaches

Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals...

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4 mg/kg/day, 14 days, prior to habituation) on the place aversion induced by two naloxone doses (1...

Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action. We recently reported that tianeptine is a full agonist at the mu opioid receptor (MOR). Here we demonstrate that the acute and chronic antidepressant-like behavioral effects of tianeptine in mice require MOR...

Substance use disorders are exceedingly complicated as is the treatment. In order to increase positive outcomes an understanding of all facets; bio, psycho/social/spiritual, economic, and interdisciplinary aspects are essential to successful treatment. There are an increasing number of integrative addictions treatment centers across the United States, and disciplines that care for this population who are committed to a holistic, integrative approach to addictions treatment. Whole-person interventions, the foundational underpinnings of complementary and integrative therapies that attend to mind, body, and spirit simultaneously, in combination with traditional health care, will serve to provide the most effective treatment and patient outcomes...

In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk...

The effects of prolonged, intermittent infusion of β-endorphin or naloxone into the third cerebral ventricle of follicular-phase ewes on the expression of genes encoding GnRH and GnRHR in the hypothalamus and GnRHR in the anterior pituitary gland (AP) were examined by an enzyme-linked immunoabsorbent assay. Activation or blockade of μ-opioid receptors significantly decreased or increased the GnRH concentration and GnRHR abundance in the hypothalamus, respectively, and affected in the same way GnRHR quantity in the AP gland...

Opioid is a popular drug of abuse and addiction. We evaluated acupuncture as a non-pharmacological treatment with a focus on managing withdrawal symptoms. Electrical stimulation at a low frequency (2 Hz) accelerates endorphin and encephalin production. High-frequency stimulation (100 Hz) up-regulates the dynorphin level that in turn suppresses withdrawal at the spinal level. The effect of 100-Hz electroacupuncture may be associated with brain-derived neurotrophic factor activation at the ventral tegmental area, down-regulation of cAMP response element-binding protein, and enhanced dynorphin synthesis in the spinal cord, periaqueductal grey, and hypothalamus...

Effective medications for drug abuse remain a largely unmet goal in biomedical science. Recently, the (+)-enantiomers of naloxone and naltrexone, TLR4 antagonists, have been reported to attenuate preclinical indicators of both opioid and stimulant abuse. To further examine the potential of these compounds as drug-abuse treatments, we extended the previous assessments to include a wider range of doses and procedures. We report the assessment of (+)-naloxone and (+)-naltrexone on the acute dopaminergic effects of cocaine and heroin determined by in vivo microdialysis, on the reinforcing effects of cocaine and the opioid agonist, remifentanil, tested under intravenous self-administration procedures, as well as the subjective effects of cocaine determined by discriminative-stimulus effects in rats...

The past decade in the U.S. has been marked by a media fascination with the white prescription opioid cum heroin user. In this paper, we contrast media coverage of white non-medical opioid users with that of black and brown heroin users to show how divergent representations lead to different public and policy responses. A content analysis of 100 popular press articles from 2001 and 2011 in which half describe heroin users and half describe prescription opioid users revealed a consistent contrast between criminalized urban black and Latino heroin injectors with sympathetic portrayals of suburban white prescription opioid users...

Persistent cocaine-induced neuroadaptations within the cortico-striatal circuitry might be related to elevated risk of relapse observed in human addicts even after months or years of drug-free abstinence. Identification of these neuroadaptations may lead development of novel, neurobiologically-based treatments of relapse. In the current study, 12 adult male Sprague-Dawley rats self-administered cocaine (or received yoked-saline) for two weeks followed by three weeks of home-cage abstinence. At this point, we analyzed expression of proteins involved in regulation of Gαi- and Gαq-protein signaling in the dorsal striatum (dSTR)...

UNLABELLED: Dependence is a hallmark feature of opiate addiction and is defined by the emergence of somatic and affective withdrawal signs. The nucleus accumbens (NAc) integrates dopaminergic and glutamatergic inputs to mediate rewarding and aversive properties of opiates. Evidence suggests that AMPA glutamate-receptor-dependent synaptic plasticity within the NAc underlies aspects of addiction. However, the degree to which NAc AMPA receptors (AMPARs) contribute to somatic and affective signs of opiate withdrawal is not fully understood...

Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippocampus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal...

Morphine is one of the most effective drugs used for pain management, but it is also highly addictive. Morphine elicits acute and long-term adaptive changes at cellular and molecular level in the brain, which play a critical role in the development of tolerance, dependence and addiction. Previous studies indicated that the dopamine D4 receptor (D4 R) activation counteracts morphine-induced adaptive changes of the μ opioid receptor (MOR) signaling in the striosomes of the caudate putamen (CPu), as well as the induction of several Fos family transcription factors...

OBJECTIVE: To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis. DATA SOURCES: A computerized literature search was conducted in MEDLINE, Embase, the Cochrane Library, SciELO, PsycINFO, Scopus, and Web of Knowledge. No year or country restrictions were used. The Boolean terms used for the electronic database search were (NAC OR N-acetylcysteine OR acetylcysteine) AND (depression OR depressive OR depressed) AND (trial)...

Decreased motivation to work for a natural reward is a sign of amphetamine withdrawal and is thought to be associated with hypofunction of the mesolimbic dopamine system. During withdrawal from repeated amphetamine administration, rats showed reduced responding for a sweet solution in a progressive ratio schedule. Repeated systemic treatment with terguride (0.2 and 0.4 mg/kg, i.p.) twice daily during the first four days of amphetamine withdrawal reversed the decrease in responding for the sweet solution. These results suggest that dopamine partial agonists, possibly due to their agonistic-like actions under these conditions, are a potential therapeutic approach for the acute withdrawal stage of the amphetamine addition cycle...

UNLABELLED: The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed...

Opioids are the most powerful analgesics. As pain is driven by sensory transmission and opioid receptors couple to inhibitory G proteins, according to the classical concept, opioids alleviate pain by activating receptors on neurons and blocking the release of excitatory mediators (e.g., substance P). Here we show that analgesia can be mediated by opioid receptors in immune cells. We propose that activation of leukocyte opioid receptors leads to the secretion of opioid peptides Met-enkephalin, β-endorphin and dynorphin A (1-17), which subsequently act at local neuronal receptors, to relieve pain...

UNLABELLED: Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses...

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, serotonin, glutamate, glutamine, aspartate, γ-aminobutyric acid, adenosine) as well as neuroactive drugs (amphetamine, sibutramine, fluvoxamine) and drug metabolites in situ directly in brain tissue sections...

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage...