Subanesthetic ketamine decreases the incentive-motivational value of reward-related cues

Fitzpatrick, Christopher; Morrow, Jonathan D.

doi:10.1177/0269881116667709

Cited by 18 publications

(16 citation statements)

References 62 publications

(90 reference statements)

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“…Several studies demonstrated anti-depressant and anti-addiction properties of ketamine. One study suggested that ketamine may be used to treat addiction by decreasing the incentive-motivational value of reward-related cues [20]. Other studies have shown a prolongation of abstinence from the use of alcohol and heroin in dependent individuals [21].…”

Section: Discussionmentioning

confidence: 99%

“…First, this study focused on the prehospital setting, and was therefore limited in its capacity to assess whether the use of ketamine may lead to dependence or addiction. However, research has reported the anti-addiction property of ketamine [ 20 - 22 ]. A prospective cohort study with a longer follow-up period is warranted to verify the anti-addiction property of ketamine reported by the research community.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Safety and Efficacy of Prehospital Paramedic Administration of Sub-Dissociative Dose of Ketamine in the Treatment of Trauma-Related Pain in Adult Civilian Population

Jabourian¹,

Dong²,

Mackey³

et al. 2020

Cureus

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Opiates are addicting and have a high potential for dependency. In the past decades, opiates remained the first-line pharmaceutical option of prehospital treatment for acute traumatic pain in the civilian population. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that has analgesic properties and may serve as an alternative agent for the treatment of acute traumatic pain in prehospital settings. This study aims to assess the safety and efficacy of ketamine administration by paramedics in civilian prehospital settings for the treatment of acute traumatic pain. This was a prospective observational study in San Bernardino, Riverside and Stanislaus counties. Patients were included if they were > 15 years of age with complaints of traumatic or burn-related pain. Patients were excluded if they received opiates up to six hours prior to or concurrently with ketamine administration. The dose administered was 0.3 mg/kg intravenously over five minutes with a maximum dose of 30 mg. The option to administer a second dose was available to paramedics if the patient continued to have pain after 15 minutes following the first administration. Paired-T tests were conducted to assess the change in the primary outcome (pain score) and secondary outcomes (e.g. systolic blood pressure, pulse, and respiratory rate). P-value<0.05 was considered to be statistically significant. A total of 368 patients were included in the final analysis. The average age was 52.9 ± 23.1 years, and the average weight was 80.4 ± 22.2 kg. There was a statistically significant reduction in the pain score (9.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Safety and Efficacy of Prehospital Paramedic Administration of Sub-Dissociative Dose of Ketamine in the Treatment of Trauma-Related Pain in Adult Civilian Population

Jabourian¹,

Dong²,

Mackey³

et al. 2020

Cureus

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“…Together our findings that account for behavior based on tracking tendency suggest that BLA-IC is necessary for supporting the initial approach directed at the preferred response location. Yet the modest effects for both food cup and lever approach behaviors suggests other brain circuits support these behaviors in the absence of BLA-IC communication (Flagel, Clark et al 2011, Saunders and Robinson 2012, Clark, Collins et al 2013, Saunders, Yager et al 2013, Chang, Todd et al 2015, Haight, Fraser et al 2015, Ahrens, Meyer et al 2016, DiFeliceantonio and Berridge 2016, Fitzpatrick, Creeden et al 2016, Fraser, Haight et al 2016, Naeem and White 2016, Sculfort, Bartsch et al 2016, Stringfield, Palmatier et al 2016, Torres, Glueck et al 2016, Versaggi, King et al 2016, Fitzpatrick and Morrow 2017, Koshy Cherian, Kucinski et al 2017, Pitchers, Phillips et al 2017, White and Naeem 2017).…”

Section: Discussionmentioning

confidence: 99%

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping

Nasser

Lafferty

Lesser

et al. 2018

Neurobiology of Learning and Memory

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Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery.

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“…Pavlovian conditioned approach: procedure. Pavlovian conditioned approach was performed as previously described 82,83 . For two days prior to pretraining, rats were familiarized with banana-flavored food pellets (45 mg; Bioserv; Frenchtown, NJ) in their home cages (25 pellets/cage).…”

Section: Animalsmentioning

confidence: 99%

Individual variation in the attribution of incentive salience to social cues

Fitzpatrick

Morrow

2020

Sci Rep

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Research on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals and addiction in humans. The influence of social cues on drug-seeking behavior has garnered attention recently, but few studies have investigated how social cues gain incentive-motivational value. In the present study, a Pavlovian conditioned approach (PCA) procedure was used to identify rats that are more (sign-trackers; STs) or less (goal-trackers; GTs) prone to attribute incentive salience to food reward cues. In Experiment 1, a novel procedure employed social 'peers' to compare the tendency of STs and GTs to attribute incentive salience to social reward cues as well as form a social-conditioned place preference. In Experiment 2, social behavior of STs and GTs was compared using social interaction and choice tests. Finally, in Experiment 3, levels of plasma oxytocin were measured in STs and GTs seven days after the last PCA training session, because oxytocin is known to modulate the mesolimbic reward system and social behavior. Compared to GTs, STs attributed more incentive salience to social-related cues and exhibited prosocial behaviors (e.g., social-conditioned place preference, increased social interaction, and social novelty-seeking). No group differences were observed in plasma oxytocin levels. Taken together, these experiments demonstrate individual variation in the attribution of incentive salience to both food-and social-related cues, which has important implications for the pathophysiology of addiction.

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Subanesthetic ketamine decreases the incentive-motivational value of reward-related cues

Cited by 18 publications

References 62 publications

Evaluation of Safety and Efficacy of Prehospital Paramedic Administration of Sub-Dissociative Dose of Ketamine in the Treatment of Trauma-Related Pain in Adult Civilian Population

Evaluation of Safety and Efficacy of Prehospital Paramedic Administration of Sub-Dissociative Dose of Ketamine in the Treatment of Trauma-Related Pain in Adult Civilian Population

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping

Individual variation in the attribution of incentive salience to social cues

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