The Third Reviewer

The last decade has witnessed the emergence of new pharmacotherapy in the treatment of drug and alcohol dependence, although addiction to the psychostimulants cocaine and amphetamines is notoriously resistant to pharmacological approaches that can effe… . . . → Read More: Stress-Related Receptor Targets for Cocaine Addiction

Background: Psychostimulants and opiates trigger similar enduring neuroadaptations within the reward circuitry thought to underlie addiction. Transcription factors are key to mediating these enduring behavioral alterations. The facilitation of these ma… . . . → Read More: Glucocorticoid Receptors in Dopaminoceptive Neurons, Key for Cocaine, Are Dispensable for Molecular and Behavioral Morphine Responses

Background: Modulation of midbrain dopamine neurons by nicotinic acetylcholine receptors (nAChRs) plays an important role in behavior, cognition, motivation, and reward. Specifically, nAChRs containing ?2 subunits (?2-nAChRs) switch dopamine cells fr… . . . → Read More: Peroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors

Background: Oral naltrexone effectively antagonizes heroin, but patient noncompliance limits its utility; sustained-release preparations may overcome this. Few data are available on optimal blood naltrexone levels for preventing craving and/or return to heroin use. This study assesses various risk factors, including blood naltrexone level, for heroin craving and relapse to illicit opioids.Methods: Heroin-dependent persons from a randomized controlled trial of oral versus implant naltrexone were followed up for 6 months. Thirty-four participants received 50 mg oral naltrexone daily, plus placebo implant; thirty-five participants received a single dose of 2.3 g naltrexone implant, plus daily oral placebo tablets.Results: Compared to oral naltrexone patients, implant naltrexone patients were significantly less likely to use any opioids and had one-fifth the risk of using heroin ? weekly. Risk of ? weekly heroin use increased by 2.5 times at blood naltrexone concentration < .5 ng/mL compared with ? .5 ng/mL, with 3 ng/mL associated with very low risk of use. Craving remained near “floor” levels for implant patients but rebounded to higher levels among oral patients. Lower craving scores (? 20/70) predicted lower relapse risk. Noncompliance with daily oral formula, higher baseline craving, longer history of use, and being younger predicted higher craving at follow-up.Conclusions: Implant naltrexone was better associated with reduced heroin craving and relapse than oral naltrexone. Effective treatment was achieved at blood naltrexone levels of 1 ng/mL to 3 ng/mL, with higher levels associated with greater efficacy. Craving assessment may be valuable in predicting relapse risk allowing timely intervention. . . . → Read More: Risk Factors for Craving and Relapse in Heroin Users Treated with Oral or Implant Naltrexone

Background: Acute and chronic stress reinstates drug-seeking behavior. Current animal models show that these effects are contingent (temporally, contextually, or both) on the drug-conditioning environment. To date, no paradigm exists to model the commo… . . . → Read More: Persistent Increases in Cocaine-Seeking Behavior After Acute Exposure to Cold Swim Stress

Cannabis, like other drugs of abuse, produces its reinforcing effects by activating the brain “reward” pathways comprising dopamine (DA) neurons in the ventral tegmental area that project to the nucleus accumbens and by increasing DA levels in the … . . . → Read More: Baclofen in Cannabis Dependence Syndrome

Background: Long-lasting increases in dendritic spine density and gene expression in the nucleus accumbens and in the ambulatory response to cocaine occur following chronic cocaine treatment. Despite numerous reports of these findings, the molecular me… . . . → Read More: Behavioral and Morphological Responses to Cocaine Require Kalirin7

Background: Optimal decision-making requires that organisms correctly evaluate both the costs and benefits of potential choices. Dopamine transmission within the nucleus accumbens (NAc) has been heavily implicated in reward-learning and decision-making… . . . → Read More: Phasic Nucleus Accumbens Dopamine Release Encodes Effort- and Delay-Related Costs

Background: Recent behavioral and psychophysiological studies have provided converging evidence for emotional dysfunction in conduct disorder (CD). Most of these studies focused on male subjects and little is known about emotional processing in female … . . . → Read More: Facial Expression Recognition, Fear Conditioning, and Startle Modulation in Female Subjects with Conduct Disorder

Background: Rats with extended daily cocaine access show escalating cocaine self-administration and behavioral signs of dependence. Regulation of glutamatergic transmission by metabotropic glutamate receptors has emerged as a mechanism in the addictive… . . . → Read More: Behavioral and Functional Evidence of Metabotropic Glutamate Receptor 2/3 and Metabotropic Glutamate Receptor 5 Dysregulation in Cocaine-Escalated Rats: Factor in the Transition to Dependence

Background: Parental alcoholism substantially raises risk for offspring alcoholism, an effect thought to be mediated by a dysregulation in impulse control. Adult alcoholics have alterations in the frontostriatal system involved in regulating impulsive … . . . → Read More: Striatal Dysfunction Marks Preexisting Risk and Medial Prefrontal Dysfunction Is Related to Problem Drinking in Children of Alcoholics

Background: Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor–like (ORL1) receptor, blocks cocaine sensitization in rats. In this study, we tested whether OFQ/N would block sensitization to the motor stimulatory and conditi… . . . → Read More: Orphanin FQ/Nociceptin Not Only Blocks but Also Reverses Behavioral Adaptive Changes Induced by Repeated Cocaine in Mice

Background: Biochemical diagnostics of ethanol intake would improve alcohol abuse treatment and have applications in clinical trial and public safety settings. Self-reporting of alcohol use has clinical utility but lacks the desired reliability. Previo… . . . → Read More: Classification of Alcohol Abuse by Plasma Protein Biomarkers

Background: Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of thi… . . . → Read More: Granular Insular Cortex Inactivation as a Novel Therapeutic Strategy for Nicotine Addiction

Background: A dual representation model of intrusive memory proposes that personally experienced events give rise to two types of representation: an image-based, egocentric representation based on sensory-perceptual features; and a more abstract, alloc… . . . → Read More: Acute Effects of Alcohol on Intrusive Memory Development and Viewpoint Dependence in Spatial Memory Support a Dual Representation Model