Beta-2 adrenergic receptors mediate stress-evoked reinstatement of cocaine-induced conditioned place preference and increases in CRF mRNA in the bed nucleus of the stria terminalis in mice. Psychopharmacology (Berl) 2014 Oct;231(20):3953-63
Date
04/04/2014Pubmed ID
24696080Pubmed Central ID
PMC8647032DOI
10.1007/s00213-014-3535-0Scopus ID
2-s2.0-84897264774 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
RATIONALE: Understanding the mechanisms responsible for stress-induced relapse is important for guiding treatment strategies aimed at minimizing the contribution of stress to addiction. Evidence suggests that these mechanisms involve interactions between noradrenergic systems and the neuropeptide corticotropin-releasing factor (CRF).
OBJECTIVES: The interaction between β-adrenergic receptors (ARs) and CRF as it relates to the reinstatement of cocaine-conditioned reward in response to a stressor was examined in mice. We hypothesized that β2-ARs are required for stress-induced activation of CRF pathways responsible for reinstatement.
METHODS: Stress-induced relapse was examined based on the re-establishment of cocaine-induced conditioned place preference (CPP; 4 × 15 mg/kg cocaine, i.p.) after extinction using forced swim (6 min at 22 °C) or an injection of the β2-AR agonist, clenbuterol (4 mg/kg, i.p.). The CRF-R1 antagonist antalarmin (10 mg/kg, i.p.) or the β2-AR antagonist ICI-118,551 (1 mg/kg, i.p.) were given 30 min prior to reinstating stimuli. Quantitative PCR was conducted in dissected bed nucleus of the stria terminalis (BNST) and amygdala, putative sources of CRF that contribute to reinstatement, to examine the effects of ICI-118,551 on swim-induced increases in CRF messenger RNA (mRNA) in mice with a cocaine history.
RESULTS: Pretreatment with ICI-118,551 or antalarmin blocked swim-induced reinstatement of CPP. Reinstatement by clenbuterol was also blocked by antalarmin. ICI-118,551 pretreatment prevented swim-induced increases in CRF mRNA in the BNST. Effects in the amygdala were not observed.
CONCLUSIONS: These findings indicate that, during stress, norepinephrine, via β2-ARs, either directly or indirectly activates CRF-releasing neurons in the BNST that interface with motivational neurocircuitry to induce reinstatement of cocaine-conditioned reward.
Author List
McReynolds JR, Vranjkovic O, Thao M, Baker DA, Makky K, Lim Y, Mantsch JRAuthor
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenergic beta-AgonistsAnimals
Behavior, Addictive
Clenbuterol
Cocaine
Cocaine-Related Disorders
Conditioning, Operant
Corticotropin-Releasing Hormone
Dopamine Uptake Inhibitors
Extinction, Psychological
Male
Mice
Pyrimidines
Pyrroles
Receptors, Adrenergic, beta-2
Receptors, Corticotropin-Releasing Hormone
Recurrence
Reward
Self Administration
Septal Nuclei
Stress, Psychological
