Behavioral predictors of individual differences in opioid addiction vulnerability as measured using i.v. self-administration in rats

2021 ◽  
Vol 221 ◽  
pp. 108561
Author(s):  
Yayi Swain ◽  
Jonathan C. Gewirtz ◽  
Andrew C. Harris
Keyword(s):  
Individual Differences ◽  
Opioid Addiction ◽  
Self Administration ◽  
Behavioral Predictors

scholarly journals Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats

2019 ◽  
Author(s):  
Yayi Swain ◽  
Peter Muelken ◽  
Annika Skansberg ◽  
Danielle Lanzdorf ◽  
Zachary Haave ◽  
...  
Keyword(s):  
Individual Differences ◽  
Drug Exposure ◽  
Opioid Addiction ◽  
Self Administration ◽  
Behavioral Measures ◽  
Acute Dependence ◽  
Individual Measure ◽  
Spontaneous Withdrawal ◽  
Relationship Of ◽  
Initial Drug

AbstractUnderstanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship of sensitivity to withdrawal from initial drug exposure and later drug use vulnerability is unclear. The goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid addiction. Rats were first tested for withdrawal sensitivity following acute injections of morphine (i.e., “acute dependence”), measured as elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during naloxone-precipitated and spontaneous withdrawal. Rats were then tested for addiction vulnerability using various measures of i.v. morphine self-administration (MSA) including acquisition, demand, extinction, and reinstatement induced by morphine, stress, and/or drug-associated cues. Greater naloxone-precipitated withdrawal across repeated morphine injections and greater peak spontaneous withdrawal severity following a single morphine injection were associated with lower addiction vulnerability on multiple MSA measures. Withdrawal-induced anhedonia predicted a wider range of MSA measures than did any individual measure of MSA itself. These data suggest that high anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid addiction vulnerability in rodents, thereby establishing one of the first behavioral measures to predict individual differences in opioid SA. This model promises to be useful for furthering our understanding of behavioral and neurobiological mechanisms underlying vulnerability to opioid addiction.

scholarly journals Fentanyl vapor self-administration model in mice to study opioid addiction

2020 ◽  
Vol 6 (32) ◽  
pp. eabc0413 ◽  
Author(s):  
K. Moussawi ◽  
M. M. Ortiz ◽  
S. C. Gantz ◽  
B. J. Tunstall ◽  
R. C. N. Marchette ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opioid Addiction ◽  
Dopamine Neurons ◽  
Drug Intake ◽  
Self Administration ◽  
Protracted Abstinence ◽  
Electrophysiological Recordings ◽  
Lower Amplitude ◽  
The Many ◽  
Intravenous Catheterization

Intravenous drug self-administration is considered the “gold standard” model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABAB receptor–dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships

1993 ◽  
Vol 32 (3) ◽  
pp. 239-246 ◽  
Author(s):  
John R. Hughes ◽  
Alison H. Oliveto ◽  
Warren K. Bickel ◽  
Stephen T. Higgins ◽  
Gary J. Badger
Keyword(s):  
Individual Differences ◽  
Self Administration

scholarly journals Individual Differences in Dopamine Cell Neuroadaptations Following Cocaine Self-Administration

2009 ◽  
Vol 66 (8) ◽  
pp. 801-803 ◽  
Author(s):  
James E. McCutcheon ◽  
Francis J. White ◽  
Michela Marinelli
Keyword(s):  
Individual Differences ◽  
Self Administration ◽  
Dopamine Cell

scholarly journals Lack of effect of different pain-related manipulations on opioid self-administration, reinstatement of opioid seeking, and opioid choice in rats

2021 ◽  
Author(s):  
David J Reiner ◽  
E Andrew Townsend ◽  
Javier Orihuel Menendez ◽  
Sarah V Applebey ◽  
Sarah M Claypool ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Pain Relief ◽  
Inflammatory Pain ◽  
Experimental Pain ◽  
Reinforcement Rate ◽  
Opioid Addiction ◽  
Self Administration ◽  
Related Factors ◽  
Behavioral Impairments ◽  
Context Specific

ABSTRACTRationale and ObjectivePain-related factors increase risk for opioid addiction, and opioid-induced pain relief may function as a negative reinforcer to increase opioid taking and seeking. However, experimental pain-related manipulations generally do not increase opioid self-administration in rodents. This discrepancy may reflect insufficient learning of pain-relief contingencies or confounding effects of pain-related behavioral impairments. Here we determined if pairing noxious stimuli with opioid self-administration would promote pain-related reinstatement of opioid seeking or increase opioid choice over food.MethodsIn Experiment 1, rats self-administered fentanyl in the presence or absence of repeated intraplantar capsaicin injections in distinct contexts to model context-specific exposure to cutaneous nociception. After capsaicin-free extinction in both contexts, we tested if capsaicin would reinstate fentanyl seeking. In Experiment 2, rats self-administered heroin after intraperitoneal (i.p.) lactic acid injections to model acute visceral inflammatory pain. After lactic acid-free extinction, we tested if lactic acid would reinstate heroin seeking. In Experiment 3, we tested if repeated i.p. lactic acid or intraplantar Complete Freund’s Adjuvant (CFA; to model sustained inflammatory pain) would increase fentanyl choice over food.ResultsIn Experiments 1-2, neither capsaicin nor lactic acid reinstated opioid seeking after extinction, and lactic acid did not increase heroin-induced reinstatement. In Experiment 3, lactic acid and CFA decreased reinforcement rate without affecting fentanyl choice.ConclusionsResults extend the range of conditions across which pain-related manipulations fail to increase opioid seeking in rats and suggest that enhanced opioid-addiction risk in humans with chronic pain involves factors other than enhanced opioid reinforcement and relapse.

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