The molecular-container calabadion-2 prevents methamphetamine-induced reinstatement in rats: A potential approach to relapse prevention?

Michael Z. Leonard, Paul Rostin, Kevin P. Hill, Stephanie D. Grabitz, Matthias Eikermann, Klaus A. Miczek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)401-405
Number of pages5
JournalInternational Journal of Neuropsychopharmacology
Volume23
Issue number6
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Methamphetamine
  • Reinstatement
  • Relapse
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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