Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to ...

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumb...

Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augment...

This study examined the role of endocannabinoid signaling in stress-induced reinstatement of cocaine seeking and explored the interaction between noradrenergic and endocannabinergic systems in the process. A well-validated preclinical model for human relapse, the rodent conditioned place preference assay, was used. Cocaine-induced place preference was established in C57BL/6 mice using injection...

Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or reconsolidation. Recently, matrix metalloproteinases (MMPs) h...

Cocaine addicts increase the frequency and amount of drug use over time. This characteristic has been modeled by escalating drug intake in rats that were given extended access to cocaine. However, it remains unclear whether the behavior of escalating drug intake or simply increased drug dose is the relevant aspect of this model. The present study investigated whether the phenomenon of escalated...

INTRODUCTIONCONCLUSIONS REFERENCESSubstance P (SP) and its preferred neurokinin-1 (NK1)receptor play a significant role in stress and anxiety-relatedbehaviors. While the influence of the NK1 receptor onstress responses is well documented, less is known aboutits role in reward and addiction. Recent studies havesuggested a critical role of the SP/NK1 system in ther...

Animal models of relapse to drug-seeking have borrowed heavily from associative learning approaches. In studies relapse-like behaviour, animals learn self-administer drugs then receive a period extinction during which they inhibit the operant response. Several triggers can produce recovery responding form basis variety models. These include passage time (spontaneous recovery), drug availability...

The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetam...

BACKGROUND Drug addiction is a chronic brain disease characterized by recurrent episodes of relapse to drug-seeking/-taking behaviors. The ventral subiculum, the primary output of the hippocampus, plays a critical role in mediating drug-seeking behavior. METHODS A d-amphetamine intravenous self-administration rat model was employed along with focal electrical stimulation of the ventral subicu...