β-adrenergic receptor mediation of stress-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: roles for β1 and β2 adrenergic receptors. J Pharmacol Exp Ther 2012 Aug;342(2):541-51
Date
05/18/2012Pubmed ID
22593095Pubmed Central ID
PMC3400797DOI
10.1124/jpet.112.193615Scopus ID
2-s2.0-84864121632 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
Stress can trigger the relapse of drug use in recovering cocaine addicts and reinstatement in rodent models through mechanisms that may involve norepinephrine release and β-adrenergic receptor activation. The present study examined the role of β-adrenergic receptor subtypes in the stressor-induced reinstatement of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in mice. Forced swim (6 min at 22°C) stress or activation of central noradrenergic neurotransmission by administration of the selective α(2) adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement in wild-type, but not β- adrenergic receptor-deficient Adrb1/Adrb2 double-knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in reinstatement in both wild-type and β-adrenergic receptor knockout mice. Stress-induced reinstatement probably involved β(2) adrenergic receptors. The β(2) adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by forced swim or BRL-44,408, whereas administration of the nonselective β-adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the β(2) adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the β(1) adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a potential cooperative role for β(1) and β(2) adrenergic receptors in stress-induced reinstatement. Overall, these findings suggest that targeting β-adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse, particularly in cocaine addicts whose drug use is stress related.
Author List
Vranjkovic O, Hang S, Baker DA, 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 NeuronsAdrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-2 Receptor Antagonists
Animals
Behavior, Addictive
Clenbuterol
Cocaine
Cocaine-Related Disorders
Conditioning, Operant
Imidazoles
Isoindoles
Isoproterenol
Male
Mice
Motor Activity
Receptors, Adrenergic, beta-1
Receptors, Adrenergic, beta-2
Stress, Physiological
Synaptic Transmission
