The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?
Amphetamine-Related Disorders
/ drug therapy
Animals
Behavior, Addictive
/ drug therapy
Behavior, Animal
/ drug effects
Disease Models, Animal
Drug-Seeking Behavior
/ drug effects
Extinction, Psychological
Heterocyclic Compounds, 4 or More Rings
/ pharmacology
Male
Methamphetamine
Rats, Long-Evans
Recurrence
Self Administration
Sulfonic Acids
/ pharmacology
Time Factors
methamphetamine
reinstatement
relapse
self-administration
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
24
09
2019
revised:
09
12
2019
accepted:
02
01
2020
pubmed:
13
6
2020
medline:
22
9
2021
entrez:
13
6
2020
Statut:
ppublish
Résumé
Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.
Sections du résumé
BACKGROUND
Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats.
METHODS
Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2.
RESULTS
Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine.
CONCLUSIONS
These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.
Identifiants
pubmed: 32531049
pii: 5856647
doi: 10.1093/ijnp/pyz070
pmc: PMC7311644
doi:
Substances chimiques
Heterocyclic Compounds, 4 or More Rings
0
Sulfonic Acids
0
calabadion 2
0
Methamphetamine
44RAL3456C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-405Subventions
Organisme : NIDA NIH HHS
ID : R01 DA031734
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.
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