Introduction to Drug Seeking

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse.

BACKGROUND Animal models of addiction suggest that the transition from incentive-driven drug use to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue control over drug seeking.

Significance We recently introduced a rat model of incubation (time-dependent increase) of oxycodone craving after voluntary abstinence induced by negative consequences of drug seeking.

RATIONALE Epigenetic regulation has been implicated in the incubation of drug craving (the time-dependent increase in drug seeking after prolonged withdrawal from drug self-administration).

Addiction is a chronically relapsing brain disorder, involving compulsive drug seeking and taking.

Drug addiction is a chronic relapsing brain disorder that is characterized by compulsive drug seeking and continued use despite negative outcomes.

Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences.

Background Substance Use Disorder is a chronic relapsing disease that is characterized by compulsive drug seeking and use, despite harmful consequences.

We show that two distinct VP DRD3+ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking.

The circuitry is selectively necessary for drug seeking includes an Action/Reward subcircuit, comprising nucleus accumbens, ventral pallidum, and ventral tegmental area, a Prefrontal subcircuit comprising prelimbic, infralimbic, and insular cortices, a Stress subcircuit comprising the central nucleus of the amygdala and the bed nucleus of the stria terminalis, and a Diencephalon circuit including lateral hypothalamus.

Addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences.

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse.

Cue-induced drug seeking was measured on withdrawal days 3 (WD3) and 30 (WD30).

Investigators have identified an analogous incubation phenomenon in rodents, in which time-dependent increases in cue-induced drug seeking are observed after abstinence from intravenous drug or palatable food self-administration.

Environmental enrichment (EE) has been proven to reduce drug seeking and the development of addiction-related behaviors in rodent models, but the effects of EE on natural reward acquisition in the form of sweet beverages are poorly understood.

Cocaine-generated silent synapses dictate the encoding, consolidation, retrieval-induced destabilization and reconsolidation of cocaine memories, and these syapses can be targeted to reduce drug seeking and relapse.

First, at the genotypic level, apathetic behavior in older HIV-1 Tg rats treated with vehicle was characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose and enhanced drug seeking for cocaine relative to control animals treated with vehicle.

RESULTS We found that rats in the 15 days FA condition showed significantly enhanced drug seeking during extinction, irrespective of sex.

In others, stressors interact with other stimuli to promote drug seeking, thereby setting the stage for relapse.

For example, acute stress engages CRF signaling in the VTA to suppress the motivation to work for food rewards and promote drug seeking behavior.

We recently found that LS is necessary for cocaine‐seeking behaviors including conditioned place preference and reinstatement of extinguished drug seeking, which involve LS input to limbic regions including ventral tegmental area (VTA) and orexin neurons in hypothalamus.

Cannabis is also a “gateway drug”; ushering users to “harder” substances of abuse and reinstating extinguished drug seeking behaviours.

Cue extinction significantly reduced drug seeking in FR-trained rats, replicating prior results, but was ineffective in SO-trained rats.

Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period.

, cues and contexts) contributes to the maintenance of addiction, as re-exposure to drug-associated stimuli can reinstate drug seeking and taking even after long periods of abstinence.

Because of these coincident neuroadaptations, we hypothesized that an odor paired with acute restraint stress would reinstate drug seeking and chose two mechanistically distinct drugs of abuse to test this hypothesis: alcohol and cocaine.

Male Sprague Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured.

NCS-Rapgef2 in the NAc is required for activation of ERK and Egr-1/Zif268 in D1 dopaminoceptive neurons after acute cocaine administration, and subsequent enhanced locomotor response and drug seeking behavior after repeated cocaine administration.

Additionally, lack of awareness of people about opioid medicines and absence of strict laws regarding sale of opioid medicines under a valid prescription allows easy availability and promotes aberrant drug seeking behaviour.

She exhibited repetitive drug seeking behaviour.

Cannabis is also a “gateway drug”; ushering users to “harder” substances of abuse and reinstating extinguished drug seeking behaviours.

The person’s self-identity is invested in narratives of recovery, and opioid use symbolises their addicted past because for practitioners, this population is at clinical risk with the potential for drug seeking behaviours.

This model can be used to study various aspects of opioid addiction including self-administration, escalation of drug intake, extinction, reinstatement, and drug seeking despite adversity.

Significance Statement Excessive risky decision-making is a hallmark of addiction, promoting ongoing drug seeking despite the risk of social, financial, and physical consequences.

We show that two distinct VP DRD3+ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking.

Rather than experimenter-imposed extinction, punishment offers the opportunity to examine reinvigorated drug seeking following voluntary abstinence.

Considering that drug seeking often depends on the association between drug-paired cues and the rewarding effects of the drug, α7 nAChRs in the mPFC could be considered as potential targets for the prevention or treatment of cocaine use disorder.

Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use.